Mitochondria: Master Regulator of Metabolism, Homeostasis, Stress, Aging and Epigenetics
Abstract
BACKGROUND: Mitochondria became a driving force in evolution due to their ability to manufacture adenosine triphosphate (ATP) through respiration. The functioning of mitochondria within eukaryotic cells has evolved dramatically as a result of evolution. Recent research has revealed mitochondria form plasticity to keep the cell's needs and function.
CONTENT: Mitochondria have long been regarded as the cell's "powerhouse," providing energy for cell metabolism through oxidative phosphorylation (OXPHOS). A lot of physiological processes were known to be mediated by mitochondria including immunity and autophagy, cell death mechanism, and stem cell reprogramming. Mitochondria can change their shape to form a tubular network that is controlled by fission and fusion processes. Mitochondrial dynamics is the equilibrium between these two opposing processes that regulates mitochondrial number, size, and positioning within the cytoplasm.
SUMMARY: All of these discoveries opened up new research avenues and revealed new targets for targeted medication development. Calorie restriction, and the mimetic agents were developed to increase mitochondria biogenesis to improve human lifespan.
KEYWORDS: mitochondria, metabolism, homeostasis, stress response, aging, epigenetic
Full Text:
PDFReferences
Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996; 86: 147–57, CrossRef.
Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001; 1: 515–25, CrossRef.
Khacho M, Clark A, Svoboda DS, Azzi J, MacLaurin JG, Meghaizel C, et al. Mitochondrial dynamics impacts stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell. 2016; 19: 232–47, CrossRef.
Yasukawa K, Oshiumi H, Takeda M, Ishihara N, Yanagi Y, Seya T, et al. Mitofusin 2 inhibits mitochondrial antiviral signaling. Sci Signal. 2009; 2: ra47, CrossRef.
Picard M, Wallace DC, Burelle Y. The rise of mitochondria in medicine. Mitochondrion. 2016; 30: 105–16, CrossRef.
Zemirli N, Morel E, Molino D. Mitochondrial dynamics in basal and stressful conditions. IJMS. 2018; 19: 564, CrossRef.
Suárez-Rivero JM, Villanueva-Paz M, De la Cruz-Ojeda P, De la Mata M, Cotán D, Oropesa-Ávila M, et al. Mitochondrial dynamics in mitochondrial diseases. diseases. 2017; 5: 1, CrossRef.
Giacomello M, Pyakurel A, Glytsou C, Scorrano L. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol. 2020; 21: 204–24, CrossRef.
Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong S-E, et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008; 134: 112–23, CrossRef.
Eisner V, Picard M, Hajnóczky G. Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol. 2018; 20: 755–65, CrossRef.
Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012; 337: 1062–5, CrossRef.
Kim TY, Wang D, Kim AK, Lau E, Lin AJ, Liem DA, et al. Metabolic labeling reveals proteome dynamics of mouse mitochondria. Mol Cell Proteomics. 2012; 11: 1586–94, CrossRef.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153: 1194–217, CrossRef.
Tseng AHH, Shieh S-S, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013; 63: 222–34, CrossRef.
Davinelli S, De Stefani D, De Vivo I, Scapagnini G. Polyphenols as caloric restriction mimetics regulating mitochondrial biogenesis and mitophagy. Trends Endocrinol Metab. 2020; 31: 536–50, CrossRef.
Sugiura A, McLelland G, Fon EA, McBride HM. A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles. EMBO J. 2014; 33: 2142–56, CrossRef.
Neuspiel M, Schauss AC, Braschi E, Zunino R, Rippstein P, Rachubinski RA, et al. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol. 2008; 18: 102–8, CrossRef.
Soubannier V, McLelland G-L, Zunino R, Braschi E, Rippstein P, Fon EA, et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 2012; 22: 135–41, CrossRef.
Soubannier V, Rippstein P, Kaufman BA, Shoubridge EA, McBride HM. Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PLoS ONE. 2012; 7: e52830, CrossRef.
Mcbride HM, Mohanty A. Emerging roles of mitochondria in the evolution, biogenesis, and function of peroxisomes. Front Physiol. 2013; 4: 268, CrossRef.
Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J. 2008; 27: 306–14, CrossRef.
Augustin S, Nolden M, Müller S, Hardt O, Arnold I, Langer T. Characterization of peptides released from mitochondria: evidence for constant proteolysis and peptide efflux. J Biol Chem. 2005; 280: 2691–9, CrossRef.
Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell. 1998 Jun; 93: 973–83, CrossRef.
Ahola S, Langer T, MacVicar T. Mitochondrial proteolysis and metabolic control. Cold Spring Harb Perspect Biol. 2019; 11: a033936, CrossRef.
Quirós PM, Langer T, López-Otín C. New roles for mitochondrial proteases in health, ageing and disease. Nat Rev Mol Cell Biol. 2015; 16: 345–59, CrossRef.
Chan NC, Chan DC. Parkin uses the UPS to ship off dysfunctional mitochondria. Autophagy. 2011; 7: 771–2, CrossRef.
Ciechanover A. Early work on the ubiquitin proteasome system, an interview with Aaron Ciechanover. Interview by CDD. Cell Death Differ. 2005; 12: 1167–77, CrossRef.
Haas AL, Siepmann TJ. Pathways of ubiquitin conjugation. FASEB J. 1997; 11: 1257–68, CrossRef.
Hoeller D, Hecker CM, Dikic I. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer. 2006; 6: 776–88, CrossRef.
Ni HM, Williams JA, Ding WX. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2015; 4: 6–13, CrossRef.
Baker MJ, Tatsuta T, Langer T. Quality control of mitochondrial proteostasis. Cold Spring Harb Perspect Biol. 2011; 3: a007559, CrossRef.
Twig G, Elorza A, Molina AJA, Mohamed H, Wikstrom JD, Walzer G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008; 27: 433–46, CrossRef.
Ding WX, Guo F, Ni HM, Bockus A, Manley S, Stolz DB, et al. Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation. J Biol Chem. 2012; 287: 42379–88, CrossRef.
Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018; 28: R170–85, CrossRef.
Campbell CT, Kolesar JE, Kaufman BA. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta Gene Regul Mech BBA – Gene Regul Mech. 2012; 1819: 921–9, CrossRef.
Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999; 98: 115–24, CrossRef.
Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000; 106: 847–56, CrossRef.
Baar K, Wende AR, Jones TE, Marison M, Nolte LA, Chen M, et al. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J. 2002; 16: 1879–86. https://doi.org/10.1096/fj.02-0367com">CrossRef.
Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol (Lond). 2003; 546: 851–8, CrossRef.
Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, et al. Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005; 1: 259–71, CrossRef.
Cogliati S, Enriquez JA, Scorrano L. Mitochondrial cristae: where beauty meets functionality. Trends Biochem Sci. 2016; 41: 261–73, CrossRef.
Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, et al. Mitochondrial bioenergetics and structural network organization. J Cell Sci. 2007; 120: 838–48, CrossRef.
Liesa M, Shirihai OS. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 2013; 17: 491–506, CrossRef.
Wai T, Langer T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol Metab. 2016; 27: 105–17, CrossRef.
Wesselink E, Koekkoek WAC, Grefte S, Witkamp RF, van Zanten ARH. Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence. Clin Nutr. 2019; 38: 982–95, CrossRef.
Tondera D, Grandemange S, Jourdain A, Karbowski M, Mattenberger Y, Herzig S, et al. SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 2009; 28: 1589–600, CrossRef.
Gomes LC, Di Benedetto G, Scorrano L. Essential amino acids and glutamine regulate induction of mitochondrial elongation during autophagy. Cell Cycle. 2011; 10: 2635–9, CrossRef.
Christie DA, Mitsopoulos P, Blagih J, Dunn SD, St-Pierre J, Jones RG, et al. Stomatin-like protein 2 deficiency in t cells is associated with altered mitochondrial respiration and defective CD4 + T cell responses. J Immunol. 2012; 189: 4349–60, CrossRef.
Mitsopoulos P, Chang YH, Wai T, König T, Dunn SD, Langer T, et al. Stomatin-like protein 2 is required for in vivo mitochondrial respiratory chain supercomplex formation and optimal cell function. Mol Cell Biol. 2015; 35: 1838–47, CrossRef.
Qiu H, Schlegel V. Impact of nutrient overload on metabolic homeostasis. Nutr Rev. 2018; 76: 693–707, CrossRef.
Lisowski P, Kannan P, Mlody B, Prigione A. Mitochondria and the dynamic control of stem cell homeostasis. EMBO Rep. 2018; 19(5): e45432, CrossRef.
Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. J Cell Biol. 2016; 212: 379–87, CrossRef.
Sebastián D, Zorzano A. Mitochondrial dynamics and metabolic homeostasis. Curr Opin Physiol. 2018; 3: 34–40, CrossRef.
Bahat A, Gross A. Mitochondrial plasticity in cell fate regulation. J Biol Chem. 2019; 294: 13852–63, CrossRef.
Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003; 160: 189–200, CrossRef.
Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, et al. The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol. 2014; 204: 919–29, CrossRef.
Ishihara N, Fujita Y, Oka T, Mihara K. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J. 2006; 25: 2966–77, CrossRef.
Baker MJ, Lampe PA, Stojanovski D, Korwitz A, Anand R, Tatsuta T, et al. Stress-induced OMA1 activation and autocatalytic turnover regulate OPA1-dependent mitochondrial dynamics. EMBO J. 2014; 33: 578–93, CrossRef.
Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J Cell Biol. 2009; 187: 959–66, CrossRef.
Duvezin-Caubet S, Jagasia R, Wagener J, Hofmann S, Trifunovic A, Hansson A, et al. Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J Biol Chem. 2006; 281: 37972–9, CrossRef.
Makino A, Suarez J, Gawlowski T, Han W, Wang H, Scott BT, et al. Regulation of mitochondrial morphology and function by O-GlcNAcylation in neonatal cardiac myocytes. Am J Physiol Regul Integr Comp Physiol. 2011; 300: R1296–302, CrossRef.
Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, et al. SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol. 2014; 34: 807–19, CrossRef.
Smirnova E, Griparic L, Shurland D-L, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. MBoC. 2001; 12: 2245–56, CrossRef.
Labbé K, Murley A, Nunnari J. Determinants and functions of mitochondrial behavior. Annu Rev Cell Dev Biol. 2014; 30: 357–91, CrossRef.
West AP, Shadel GS, Ghosh S. Mitochondria in innate immune responses. Nat Rev Immunol. 2011; 11: 389–402, CrossRef.
Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011; 469: 221–5, CrossRef.
Iyer SS, He Q, Janczy JR, Elliott EI, Zhong Z, Olivier AK, et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity. 2013; 39: 311–23, CrossRef.
Park S, Won JH, Hwang I, Hong S, Lee HK, Yu JW. Defective mitochondrial fission augments NLRP3 inflammasome activation. Sci Rep. 2015; 5: 15489, CrossRef.
Wong YC, Ysselstein D, Krainc D. Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature. 2018; 554: 382–6, CrossRef.
Schmitt K, Grimm A, Dallmann R, Oettinghaus B, Restelli LM, Witzig M, et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. 2018; 27: 657-666.e5, CrossRef.
Tilokani L, Nagashima S, Paupe V, Prudent J. Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem. 2018; 62: 341–60, CrossRef.
Tait SWG, Green DR. Mitochondria and cell signalling. J Cell Sci. 2012; 125: 807–15, CrossRef.
Settembre C, Fraldi A, Medina DL, Ballabio A. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol. 2013; 14: 283–96, CrossRef.
Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2020; 21: 101–18, CrossRef.
Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018; 19: 121–35, CrossRef.
Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab. 2012; 23: 459–66, CrossRef.
Quirós PM, Mottis A, Auwerx J. Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol. 2016; 17: 213–26, CrossRef.
Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009; 458: 1056–60, CrossRef.
Cantó C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, et al. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab. 2010; 11: 213–9, CrossRef.
Garcia-Roves PM, Osler ME, Holmström MH, Zierath JR. Gain-of-function R225Q mutation in AMP-activated protein kinase γ3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J Biol Chem. 2008; 283: 35724–34, CrossRef.
Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science. 2002; 296: 349–52, CrossRef.
Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005; 2: 21–33, CrossRef.
Jazwinski SM. The retrograde response: When mitochondrial quality control is not enough. Biochim Biophys Acta Mol Cell Res. 2013; 1833: 400–9, CrossRef.
Andreux PA, Houtkooper RH, Auwerx J. Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov. 2013; 12: 465–83, CrossRef.
Friedman JR, Nunnari J. Mitochondrial form and function. Nature. 2014; 505: 335–43, CrossRef.
Crozet P, Margalha L, Confraria A, Rodrigues A, Martinho C, Adamo M, et al. Mechanisms of regulation of SNF1/AMPK/SnRK1 protein kinases. Front Plant Sci. 2014; 5: 190, CrossRef.
Inoki K, Zhu T, Guan K-L. TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003; 115: 577–90, CrossRef.
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30: 214–26, CrossRef.
Carling D, Zammit VA, Hardie DG. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 1987; 223: 217–22, CrossRef.
Munday MR, Campbell DG, Carling D, Hardie DG. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur J Biochem. 1988; 175: 331–8, CrossRef.
Marsin AS, Bertrand L, Rider MH, Deprez J, Beauloye C, Vincent MF, et al. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol. 2000; 10: 1247–55, CrossRef.
Bando H. Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer. Clin Cancer Res. 2005; 11: 5784–92, CrossRef.
Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA. 2007; 104: 12017–22, CrossRef.
Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011; 331: 456–61, CrossRef.
Berridge MJ, Bootman MD, Lipp P. Calcium--a life and death signal. Nature. 1998; 395: 645–8, CrossRef.
Kamer KJ, Mootha VK. The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol. 2015; 16: 545–53, CrossRef.
Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015; 163: 560–9, CrossRef.
Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 2015; 88: 179–88, CrossRef.
Wild AC, Moinova HR, Mulcahy RT. Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem. 1999; 274: 33627–36, CrossRef.
Sasaki H, Sato H, Kuriyama-Matsumura K, Sato K, Maebara K, Wang H, et al. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J Biol Chem. 2002; 277: 44765–71, CrossRef.
Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 2002; 62: 5196–203, PMID.
Ushida Y, Talalay P. sulforaphane accelerates acetaldehyde metabolism by inducing aldehyde dehydrogenases: relevance to ethanol intolerance. Alcohol Alcohol. 2013; 48: 526–34. https://doi.org/10.1093/alcalc/agt063">CrossRef.
Holmström KM, Baird L, Zhang Y, Hargreaves I, Chalasani A, Land JM, et al. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration. Biol Open. 2013; 2: 761–70, CrossRef.
Greco T, Fiskum G. Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition. J Bioenerg Biomembr. 2010; 42: 491–7, CrossRef.
Picard M, McEwen BS, Epel ES, Sandi C. An energetic view of stress: focus on mitochondria. Front Neuroendocrinol. 2018; 49: 72–85, CrossRef.
Lemasters JJ. Rusty notions of cell injury. J Hepatol. 2004; 40: 696–8, CrossRef.
Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012; 13: 566–78, CrossRef.
Bagur R, Hajnóczky G. Intracellular Ca2+ sensing: its role in calcium homeostasis and signaling. Mol Cell. 2017; 66: 780–8, CrossRef.
Holmström KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 2014; 15: 411–21, CrossRef.
Liu X, Hajnóczky G. Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ. 2011; 18: 1561–72, CrossRef.
Zemirli N, Pourcelot M, Ambroise G, Hatchi E, Vazquez A, Arnoult D. Mitochondrial hyperfusion promotes NF-κB activation via the mitochondrial E3 ligase MULAN. FEBS J. 2014; 281: 3095–112, CrossRef.
Kikis EA, Gidalevitz T, Morimoto RI. Protein homeostasis in models of aging and age-related conformational disease. Adv Exp Med Biol. 2010; 694: 138–59, CrossRef.
Vabulas RM, Raychaudhuri S, Hayer-Hartl M, Hartl FU. Protein folding in the cytoplasm and the heat shock response. Cold Spring Harb Perspect Biol. 2010; 2: a004390, CrossRef.
Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334: 1081–6, CrossRef.
Haynes CM, Ron D. The mitochondrial UPR - protecting organelle protein homeostasis. J Cell Sci. 2010; 123: 3849–55, CrossRef.
Jovaisaite V, Mouchiroud L, Auwerx J. The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol. 2014; 217: 137–43, CrossRef.
Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000; 6: 1099–108, CrossRef.
Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003; 11: 619–33, CrossRef.
Donnelly N, Gorman AM, Gupta S, Samali A. The eIF2α kinases: their structures and functions. Cell Mol Life Sci. 2013; 70: 3493–511, CrossRef.
Palam LR, Baird TD, Wek RC. Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J Biol Chem. 2011; 286: 10939–49, CrossRef.
Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011; 144: 79–91, CrossRef.
Rathmell JC, Thompson CB. Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell. 2002; 109: S97–107, CrossRef.
Sedger LM, Katewa A, Pettersen AK, Osvath SR, Farrell GC, Stewart GJ, et al. Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice. Blood. 2010; 115: 3258–68, CrossRef.
Su JH, Deng G, Cotman CW. Bax protein expression is increased in Alzheimer’s brain: correlations with DNA damage, Bcl-2 expression, and brain pathology. J Neuropathol Exp Neurol. 1997; 56: 86–93, CrossRef.
Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, et al. REST and stress resistance in ageing and Alzheimer’s disease. Nature. 2014; 507: 448–54, CrossRef.
Honarpour N, Gilbert SL, Lahn BT, Wang X, Herz J. Apaf-1 deficiency and neural tube closure defects are found in fog mice. PNAS. 2001; 98: 9683–7, CrossRef.
Ke FFS, Vanyai HK, Cowan AD, Delbridge ARD, Whitehead L, Grabow S, et al. Embryogenesis and adult life in the absence of intrinsic apoptosis effectors BAX, BAK, and BOK. Cell. 2018; 173: 1217-1230.e17, CrossRef.
Knudson CM, Tung KSK, Tourtellotte WG, Brown GAJ, Korsmeyer SJ. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 1995; 270: 96–9, CrossRef.
Eischen CM, Roussel MF, Korsmeyer SJ, Cleveland JL. Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol. 2001; 21: 7653–62, CrossRef.
Luke JJ, van de Wetering CI, Knudson CM. Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability. Cell Death Differ. 2003; 10: 740–8, CrossRef.
Los M, Van de Craen M, Penning LC, Schenk H, Westendorp M, Baeuerle PA, et al. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 1995; 375: 81–3, CrossRef.
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018; 25: 486–541, CrossRef.
Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019; 20: 175–93, CrossRef.
Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 2020; 21: 85–100, CrossRef.
Ernster L, Schatz G. Mitochondria: a historical review. J Cell Biol. 1981; 91: 227s–55s, CrossRef.
Riera CE, Dillin A. Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol. 2015; 17: 196–203, CrossRef.
Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science. 2012; 337: 587–90, CrossRef.
Nagaraj R, Sharpley MS, Chi F, Braas D, Zhou Y, Kim R, et al. Nuclear localization of mitochondrial TCA cycle enzymes as a critical step in mammalian zygotic genome activation. Cell. 2017; 168: 210-223.e11, CrossRef.
Kourtis N, Tavernarakis N. Cellular stress response pathways and ageing: intricate molecular relationships. EMBO J. 2011; 30: 2520–31, CrossRef.
Haigis MC, Yankner BA. The aging stress response. Mol Cell. 2010; 40: 333–44, CrossRef.
Holzenberger M, Dupont J, Ducos B, Leneuve P, Géloën A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003; 421: 182–7, CrossRef.
Gems D, Partridge L. Stress-response hormesis and aging: “that which does not kill us makes us stronger.” Cell Metab. 2008; 7: 200–3, CrossRef.
Meiliana A, Wijaya A. Hormesis in health and disease: molecular mechanisms. Indones Biomed J. 2020; 12: 288–303, CrossRef.
Koppen M, Langer T. Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases. Crit Rev Biochem Mol Biol. 2007; 42: 221–42, CrossRef.
Anand R, Langer T, Baker MJ. Proteolytic control of mitochondrial function and morphogenesis. Biochim Biophys Acta. 2013; 1833: 195–204, CrossRef.
Rugarli EI, Langer T. Mitochondrial quality control: a matter of life and death for neurons. EMBO J. 2012; 31: 1336–49, CrossRef.
Baker BM, Haynes CM. Mitochondrial protein quality control during biogenesis and aging. Trends Biochem Sci. 2011; 36: 254–61, CrossRef.
Lionaki E, Tavernarakis N. Oxidative stress and mitochondrial protein quality control in aging. J Proteomics. 2013; 92: 181–94, CrossRef.
Salama R, Sadaie M, Hoare M, Narita M. Cellular senescence and its effector programs. Genes Dev. 2014; 28: 99–114, CrossRef.
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev. 2010; 24: 2463–79, CrossRef.
Herranz N, Gil J. Mitochondria and senescence: new actors for an old play. EMBO J. 2016; 35: 701–2, CrossRef.
Vasileiou P, Evangelou K, Vlasis K, Fildisis G, Panayiotidis M, Chronopoulos E, et al. Mitochondrial homeostasis and cellular senescence. Cells. 2019; 8: 686, CrossRef.
Chapman J, Fielder E, Passos JF. Mitochondrial dysfunction and cell senescence: deciphering a complex relationship. FEBS Lett. 2019; 593: 1566–79, CrossRef.
Gorgoulis VG, Pefani D-E, Pateras IS, Trougakos IP. Integrating the DNA damage and protein stress responses during cancer development and treatment. J Pathol. 2018; 246: 12–40, CrossRef.
Park SY, Choi B, Cheon H, Pak YK, Kulawiec M, Singh KK, et al. Cellular aging of mitochondrial DNA-depleted cells. Biochem Biophys Res Commun. 2004; 325: 1399–405, CrossRef.
Kelly DP, Scarpulla R. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004; 18: 357–68, CrossRef.
White FA, Bunn CL. Restriction enzyme analysis of mitochondrial DNA in aging human cells. Mech Ageing Dev. 1985; 30: 153–68, CrossRef.
Garesse R, Vallejo CG. Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene. 2001; 263: 1–16, CrossRef.
Andersson SGE, Karlberg O, Canbäck B, Kurland CG. On the origin of mitochondria: a genomics perspective. Philos Trans R Soc Lond B Biol Sci. 2003; 358: 165–77, CrossRef.
Taanman JW. The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta Bioenerg. 1999; 1410: 103–23, CrossRef.
Gerhold JM, Cansiz-Arda Ş, Lõhmus M, Engberg O, Reyes A, van Rennes H, et al. Human mitochondrial DNA-protein complexes attach to a cholesterol-rich membrane structure. Sci Rep. 2015; 5: 15292, CrossRef.
Kasashima K, Endo H. Interaction of human mitochondrial transcription factor A in mitochondria: its involvement in the dynamics of mitochondrial DNA nucleoids. Genes Cells. 2015; 20: 1017–27, CrossRef.
van de Ven RAH, Santos D, Haigis MC. Mitochondrial sirtuins and molecular mechanisms of aging. Trends Mol Med. 2017; 23: 320–31, CrossRef.
Li X, Egervari G, Wang Y, Berger SL, Lu Z. Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat Rev Mol Cell Biol. 2018; 19: 563–78, CrossRef.
Cheng X. Structural and functional coordination of DNA and histone methylation. Cold Spring Harb Perspect Biol. 2014; 6: a018747, CrossRef.
Berger SL. The complex language of chromatin regulation during transcription. Nature. 2007; 447: 407–12, CrossRef.
Schvartzman JM, Thompson CB, Finley LWS. Metabolic regulation of chromatin modifications and gene expression. Int J Cell Biol. 2018; 217: 2247–59, CrossRef.
Chantranupong L, Wolfson RL, Sabatini DM. Nutrient-sensing mechanisms across evolution. Cell. 2015; 161: 67–83, CrossRef.
Shyh-Chang N, Daley GQ, Cantley LC. Stem cell metabolism in tissue development and aging. Development. 2013; 140: 2535–47, CrossRef.
Shyh-Chang N, Ng HH. The metabolic programming of stem cells. Genes Dev. 2017; 31: 336–46, CrossRef.
Riester M, Xu Q, Moreira A, Zheng J, Michor F, Downey RJ. The Warburg effect: persistence of stem-cell metabolism in cancers as a failure of differentiation. Ann Oncol. 2018; 29: 264–70, CrossRef.
Ma T, Li J, Xu Y, Yu C, Xu T, Wang H, et al. Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming. Nat Cell Biol. 2015; 17: 1379–87, CrossRef.
Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A, Chen YC, et al. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012; 337: 96–100, CrossRef.
Herzig S, Raemy E, Montessuit S, Veuthey JL, Zamboni N, Westermann B, et al. Identification and functional expression of the mitochondrial pyruvate carrier. Science. 2012; 337: 93–6, CrossRef.
Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, et al. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014; 56: 400–13, CrossRef.
Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P, Tanner J, et al. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat Cell Biol. 2017; 19: 1027–36, CrossRef.
Wang J, Alexander P, Wu L, Hammer R, Cleaver O, McKnight SL. Dependence of mouse embryonic stem cells on threonine catabolism. Science. 2009; 325: 435–9, CrossRef.
TeSlaa T, Chaikovsky AC, Lipchina I, Escobar SL, Hochedlinger K, Huang J, et al. α-ketoglutarate accelerates the initial differentiation of primed human pluripotent stem cells. Cell Metab. 2016; 24: 485–93, CrossRef.
Moussaieff A, Rouleau M, Kitsberg D, Cohen M, Levy G, Barasch D, et al. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015; 21: 392–402, CrossRef.
Sivanand S, Viney I, Wellen KE. Spatiotemporal control of acetyl-CoA metabolism in chromatin regulation. Trends Biochem Sci. 2018; 43: 61–74, CrossRef.
Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science. 2009; 324: 1076–80, CrossRef.
Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012; 148: 1145–59, CrossRef.
Smith RAJ, Hartley RC, Cochemé HM, Murphy MP. Mitochondrial pharmacology. Trends Pharmacol Sci. 2012; 33: 341–52, CrossRef.
Whitaker RM, Corum D, Beeson CC, Schnellmann RG. Mitochondrial biogenesis as a pharmacological target: a new approach to acute and chronic diseases. Annu Rev Pharmacol Toxicol. 2016; 56: 229–49, CrossRef.
Murphy MP, Hartley RC. Mitochondria as a therapeutic target for common pathologies. Nat Rev Drug Discov. 2018; 17: 865–86, CrossRef.
Koopman WJH, Distelmaier F, Esseling JJ, Smeitink JAM, Willems PHGM. Computer-assisted live cell analysis of mitochondrial membrane potential, morphology and calcium handling. Methods. 2008; 46: 304–11, CrossRef.
Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J. 2017; 38: 774–84, CrossRef.
Waldman M, Cohen K, Yadin D, Nudelman V, Gorfil D, Laniado-Schwartzman M, et al. Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving ‘SIRT1 and PGC-1α.’ Cardiovasc Diabetol. 2018; 17: 111, CrossRef.
Kim DH, Park MH, Ha S, Bang EJ, Lee Y, Lee AK, et al. Anti-inflammatory action of β-hydroxybutyrate via modulation of PGC-1α and FoxO1, mimicking calorie restriction. Aging. 2019; 11: 1283–304, CrossRef.
Alcocer-Gómez E, Garrido-Maraver J, Bullón P, Marín-Aguilar F, Cotán D, Carrión AM, et al. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. Biochim Biophys Acta Mol Basis Dis. 2015; 1852: 1257–67, CrossRef.
Silvestre MFP, Viollet B, Caton PW, Leclerc J, Sakakibara I, Foretz M, et al. The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions. Life Sciences. 2014; 100: 55–60, CrossRef.
Kobayashi M, Takeda K, Narita T, Nagai K, Okita N, Sudo Y, et al. Mitochondrial intermediate peptidase is a novel regulator of sirtuin-3 activation by caloric restriction. FEBS Letters. 2017; 591: 4067–73, CrossRef.
López-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, et al. Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA. 2006; 103: 1768–73, CrossRef.
Hancock CR, Han D-H, Higashida K, Kim SH, Holloszy JO. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J. 2011; 25: 785–91, CrossRef.
Lanza IR, Zabielski P, Klaus KA, Morse DM, Heppelmann CJ, Bergen HR, et al. Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. Cell Metab. 2012; 16: 777–88, CrossRef.
Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012; 13: 225–38, CrossRef.
Toiber D, Sebastian C, Mostoslavsky R. Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance. Handb Exp Pharmacol. 2011; 206: 189–224, CrossRef.
Fernandez-Marcos PJ, Auwerx J. Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr. 2011; 93: 884S–90, CrossRef.
Nakagawa T, Guarente L. SnapShot: sirtuins, NAD, and aging. Cell Metab. 2014; 20: 192-192.e1, CrossRef.
Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, et al. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 2001; 107: 137–48, CrossRef.
Vaziri H, Dessain SK, Eaton EN, Imai S-I, Frye RA, Pandita TK, et al. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell. 2001; 107: 149–59, CrossRef.
Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23: 2369–80, CrossRef.
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434: 113–8, CrossRef.
Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010; 24: 1403–17, CrossRef.
Tanner KG, Landry J, Sternglanz R, Denu JM. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA. 2000; 97: 14178–82, CrossRef.
Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem. 2002; 277: 45099–107, CrossRef.
Landry J, Slama JT, Sternglanz R. Role of NAD(+) in the deacetylase activity of the SIR2-like proteins. Biochem Biophys Res Commun. 2000; 278: 685–90, CrossRef.
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425: 191–6, CrossRef.
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007; 450: 712–6, CrossRef.
Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard BP, et al. SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem. 2010; 285: 32695–703, CrossRef.
Hubbard BP, Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014; 35: 146–54, CrossRef.
Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016; 17: 679–90, CrossRef.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric restriction mimetics against age-associated disease: targets, mechanisms, and therapeutic potential. Cell Metab. 2019; 29: 592–610, CrossRef.
Chung JH, Manganiello V, Dyck JRB. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol. 2012; 22: 546–54, CrossRef.
Cao W, Dou Y, Li A. Resveratrol boosts cognitive function by targeting SIRT1. Neurochem Res. 2018; 43: 1705–13, CrossRef.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444: 337–42, CrossRef.
Kim SK, Joe Y, Zheng M, Kim HJ, Yu JK, Cho GJ, et al. Resveratrol induces hepatic mitochondrial biogenesis through the sequential activation of nitric oxide and carbon monoxide production. Antioxid Redox Signal. 2013; 20: 2589–605, CrossRef.
Cao K, Zheng A, Xu J, Li H, Liu J, Peng Y, et al. AMPK activation prevents prenatal stress-induced cognitive impairment: Modulation of mitochondrial content and oxidative stress. Free Radic Biol Med. 2014; 75: 156–66, CrossRef.
Vargas-Ortiz K, Pérez-Vázquez V, Macías-Cervantes MH. Exercise and sirtuins: a way to mitochondrial health in skeletal muscle. Int J Mol Sci. 2019; 20: 2717, CrossRef.
Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015; 350: 1208–13, CrossRef.
Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000; 403: 795–800, CrossRef.
Chini EN. Of mice and men: NAD+ boosting with niacin provides hope for mitochondrial myopathy patients. Cell Metab. 2020; 31: 1041–3, CrossRef.
Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metab. 2012; 15: 838–47, CrossRef.
Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004; 305: 1010–3, CrossRef.
Sasaki Y, Araki T, Milbrandt J. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy. J Neurosci. 2006; 26: 8484–91, CrossRef.
Katsyuba E, Auwerx J. Modulating NAD+ metabolism, from bench to bedside. EMBO J. 2017; 36: 2670–83, CrossRef.
DOI: https://doi.org/10.18585/inabj.v13i3.1616
Copyright (c) 2021 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
