Abstract
The circadian clock promotes metabolic efficiency by pre-programmed regulation of metabolic pathways in anticipation of the upcoming feeding/fasting cycle. Recent studies have suggested that the master circadian regulators Bmal1/Clock play an important role in controlling mitochondrial function, including oxidative metabolism and mitochondrial dynamics . The latter includes mitochondrial fusion, fission, and selective autophagy (mitophagy ) that follows fission. These processes not only allow mitochondria to undergo architectural/organizational changes in response to different nutrient conditions but also ensure quality control by removing damaged components through mitophagy . Results from mouse genetic models indicate that Bmal1-dependent regulation of fission and mitophagy genes reduces oxidative stress and maintains metabolic flexibility in the liver. In addition, aha-1, a C. elegans Bmal1 homologue, is required for orderly organizations of muscle mitochondria. Interestingly, Baml1 whole body knockout mice develop premature aging phenotypes, while AHA-1 over-expression increases lifespan in worms. Given that mitochondrial dysfunction appears to be a common feature associated with aging, obesity , and related metabolic diseases , these findings implicate an evolutionarily conserved regulatory mechanism that links mitochondrial fidelity to lifespan and/or healthspan.
Keywords
- Mitochondrial dynamics
- Mitophagy
- Metabolic diseases
- Oxidative stress
- Electron transport chain
- Circadian rhythm
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Alers S, Löffler AS, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32(1):2–11
Alexander C, Votruba M, Pesch UEA, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26(2):211–215
Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134(2):317–328
Atger F, Gobet C, Marquis J, Martin E, Wang J, Weger B, Lefebvre G, Descombes P, Naef F, Gachon F (2015) ‘Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver. Proc Natl Acad Sci U S A 112(47):E6579–E6588
Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330(6009):1349–1354
Bernhardt D, Müller M, Reichert AS, Osiewacz HD (2015) Simultaneous impairment of mitochondrial fission and fusion reduces mitophagy and shortens replicative lifespan. Sci Rep 5:7885
Braun RJ, Westermann B (2011) Mitochondrial dynamics in yeast cell death and aging. Biochem Soc Trans 39(5):1520
Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125(7):1241–1252
Chang CR, Blackstone C (2010) Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci 1201(1):34–39
Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280(28):26185–26192
Chen H, McCaffery JM, Chan DC (2007) ‘Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130(3):548–562
Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, Chan DC (2010) Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141(2):280–289
Chen Y, Dorn GW (2013) PINK1- phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria. Science 340(6131):471–475
Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441(7097):1162–1166
Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel CP (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26(2):207–210
Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso MA, Nijtmans L, Nedergaard J, Cannon B, Larsson NG, Trifunovic A (2009) Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab 10(2):131–138
Egan DF, Shackelford DB, Mihaylova MM, Gelino SR, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461
Egner A, Jakobs S, Hell SW (2002) Fast 100-nm resolution three-dimensional microscope reveals structural plasticity of mitochondria in live yeast. Proc Natl Acad Sci U S A 99(6):3370–3375
Glick D, Zhang W, Beaton M, Marsboom G, Gruber M, Simon MC, Hart J, Dorn GW, Brady MJ, Macleod KF (2012) BNip3 regulates mitochondrial function and lipid metabolism in the liver. Mol Cell Biol 32(13):2570–2584
Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13(5):589–598
Gong C, Li C, Qi X, Song Z, Wu J, Hughes ME, Li X (2015) The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver. Chronobiol Int 32(9):1254–1263
Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 333(6046):1109–1112
Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ (2013) Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell 49(1):186–199
Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer T, Someya S, Miyakawa T, Nakayama C, Samhan-Arias AK, Servais S, Barger JL, Portero-Otín M, Tanokura M, Prolla TA and Leeuwenburgh C (2010) Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS ONE. doi:10.1371/journal.pone.0011468
Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, Stančáková A, Goetzman E, Lam MM, Schwer B, Stevens RD, Muehlbauer MJ, Kakar S, Bass NM, Kuusisto J, Laakso M, Alt FW, Newgard CB, Farese RV, Kahn CR, Verdin E (2011) SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 44(2):177–190
Houtkooper RH, Mouchiroud L, Ryu D, Moullan N, Katsyuba E, Knott G, Williams RW, Auwerx J (2013) Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497(7450):451–457
Jacobi D, Liu S, Burkewitz K, Kory N, Knudsen NH, Alexander RK, Unluturk U, Li X, Kong X, Hyde AL, Gangl MR, Mair WB, Lee CH (2015) Hepatic Bmal1 regulates rhythmic mitochondrial dynamics and promotes metabolic fitness. Cell Metab 22(4):709–720
Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD (2010) Mitochondrial proton and electron leaks. Essays Biochem 47:53–67
Jouffe C, Cretenet G, Symul L, Martin E, Atger F, Naef F, Gachon F (2013) The circadian clock coordinates ribosome biogenesis. PLoS Biol. doi:10.1371/journal.pbio.1001455
Kageyama Y, Zhang Z, Sesaki H (2011) Mitochondrial division: molecular machinery and physiological functions. Curr Opin Cell Biol 23(4):427–434
Khapre RV, Kondratova AA, Patel S, Dubrovsky Y, Wrobel M, Antoch MP, Kondratov RV (2014) BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging 6(1):48–57
Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392(6676):605–608
Koike N, Yoo SH, Huang HC, Kumar V, Lee C, Kim TK, Takahashi JS (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338(6105):349–354
Kojima S, Sher-Chen EL, Green CB (2012) Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression. Genes Dev 26(24):2724–2736
Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20(14):1868–1873
Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510(7503):162–166
Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309(5733):481–484
Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326(5951):437–440
Liesa M, Shirihai Orian S (2013) Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 17(4):491–506
Linnane A, Ozawa T, Marzuki S, Tanaka M (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 333(8639):642–645
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217
Losón OC, Song Z, Chen H, Chan DC (2013) Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 24(5):659–667
Marcheva B, Ramsey KM, Peek CB, Affinati A, Maury E, Bass J (2013) Circadian clocks and metabolism. Handb Exp Pharmacol 217:127–155
McQuibban GA, Lee JR, Zheng L, Juusola M, Freeman M (2006) Normal mitochondrial dynamics requires rhomboid-7 and affects drosophila lifespan and neuronal function. Curr Biol 16(10):982–989
Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191(4784):144–148
Mitchell P, Moyle J (1967) Chemiosmotic hypothesis of oxidative phosphorylation. Nature 213(5072):137–139
Moullan N, Mouchiroud L, Wang X, Ryu D, Williams Evan G, Mottis A, Jovaisaite V, Frochaux Michael V, Quiros Pedro M, Deplancke B, Houtkooper RH, Riekelt H, Auwerx J (2015) Tetracyclines disturb mitochondrial function across eukaryotic models: a call for caution in biomedical research. Cell Rep 10(10):1681–1691
Nakada K, Inoue K, Ono T, Isobe K, Ogura A, Goto YI, Nonaka I, Hayashi JI (2001) Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med 7(8):934–940
Neufeld-Cohen A, Robles MS, Aviram R, Manella G, Adamovich Y, Ladeuix B, Nir D, Rousso-Noori L, Kuperman Y, Golik M (2016) Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. Proc Natl Acad Sci U S A 113(12):E1673–E1682
Nobes CD, Brown GC, Olive PN, Brand MD (1990) Non-ohmic proton conductance of the mitochondrial inner membrane in hepatocytes. J Biol Chem 265(22):12903–12909
Palikaras K, Lionaki E, Tavernarakis N (2015) Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature 521(7553):525–528
Park CB, Larsson NG (2011) Mitochondrial DNA mutations in disease and aging. J Cell Biol 193(5):809–818
Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C, Levine DC, Bacsik DJ, Gius D, Newgard CB, Goetzman E, Chandel NS, Denu JM, Mrksich M, Bass J (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342(6158):1243417
Pimenta de Castro I, Costa AC, Lam D, Tufi R, Fedele V, Moisoi N, Dinsdale D, Deas E, Loh SHY, Martins LM (2012) Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster. Cell Death Differ 19(8):1308–1316
Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, Takahashi JS, Imai SI, Bass J (2009) Circadian clock feedback cycle through NAMPT-mediated NAD(+) biosynthesis. Science 324(5927):651–654
Rana A, Rera M, Walker DW (2013) Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A 110(21):8638–8643
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1[alpha] and SIRT1. Nature 434(7029):113–118
Rojo M, Legros F, Chateau D, Lombès A (2002) Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci 115(8):1663–1674
Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, Archer SL, Chan DC, Gupta MP (2014) SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol 34(5):807–819
Santel A, Fuller MT (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114(5):867–874
Schiavi A, Maglioni S, Palikaras K, Shaik A, Strappazzon F, Brinkmann V, Torgovnick A, Castelein N, De Henau S, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N (2015) Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr Biol 25(14):1810–1822
Schon EA, Gilkerson RW (2010) Functional complementation of mitochondrial DNAs: mobilizing mitochondrial genetics against dysfunction. Biochim Biophys Acta 1800(3):245–249
Shutt T, Geoffrion M, Milne R, McBride HM (2012) The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep 13(10):909–915
Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191(7):1367–1380
Toyama EQ, Herzig S, Courchet J, Lewis TL, Losón OC, Hellberg K, Young NP, Chen H, Polleux F, Chan DC, Shaw RJ (2016) AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 351(6270):275–281
Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429(6990):417–423
Ulgherait M, Rana A, Rera M, Graniel J, Walker DW (2014) AMPK modulates tissue and organismal aging in a cell-non-autonomous manner. Cell Rep 8(6):1767–1780
Valente EM, Abou-Sleiman PM, Caputo V, Muqit MMK, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304(5674):1158
Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA, Loeb LA (2008) DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet 40(4):392–394
Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359
Westermann B (2010) Mitochondrial dynamics in model organisms: What yeasts, worms and flies have taught us about fusion and fission of mitochondria. Semin Cell Dev Biol 21(6):542–549
Wikstrom JD, Mahdaviani K, Liesa M, Sereda SB, Si Y, Las G, Twig G, Petrovic N, Zingaretti C, Graham A, Cinti S, Corkey BE, Cannon B, Nedergaard J, Shirihai OS (2014) Hormone-induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure. EMBO J 33(5):418–436
Yang CC, Chen D, Lee SS, Walter L (2011) The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate to modulate C elegans longevity. Aging Cell 10(4):724–728
Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12(1):9–14
Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337(6098):1062–1065
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327(5968):1000–1004
Acknowledgements
D. Jacobi and F. Atger are supported by the INSERM ATIP-Avenir program and by a grant from the Genavie foundation. C-.H. Lee is supported by American Diabetes Association grant 1-14-BS-122, American Heart Association grant 16GRNT31460005, and NIH grant R01DK113791.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Jacobi, D., Atger, F., Lee, CH. (2017). Circadian Control of Mitochondrial Dynamics and Its Implication in Aging. In: Jazwinski, S., Belancio, V., Hill, S. (eds) Circadian Rhythms and Their Impact on Aging. Healthy Ageing and Longevity, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-64543-8_7
Download citation
DOI: https://doi.org/10.1007/978-3-319-64543-8_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-64542-1
Online ISBN: 978-3-319-64543-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)