Metabolic control of mitophagy.
AMPK
NAD
acetyl-CoA
ageing
ageing-related disease
metabolism
mitophagy
spermidine
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
revised:
09
11
2023
received:
03
10
2023
accepted:
20
11
2023
medline:
2
12
2023
pubmed:
2
12
2023
entrez:
2
12
2023
Statut:
aheadofprint
Résumé
Mitochondrial dysfunction is a major hallmark of ageing and related chronic disorders. Controlled removal of damaged mitochondria by the autophagic machinery, a process known as mitophagy, is vital for mitochondrial homeostasis and cell survival. The central role of mitochondria in cellular metabolism places mitochondrial removal at the interface of key metabolic pathways affecting the biosynthesis or catabolism of acetyl-coenzyme A, nicotinamide adenine dinucleotide, polyamines, as well as fatty acids and amino acids. Molecular switches that integrate the metabolic status of the cell, like AMP-dependent protein kinase, protein kinase A, mechanistic target of rapamycin and sirtuins, have also emerged as important regulators of mitophagy. In this review, we discuss how metabolic regulation intersects with mitophagy. We place special emphasis on the metabolic regulatory circuits that may be therapeutically targeted to delay ageing and mitochondria-associated chronic diseases. Moreover, we identify outstanding knowledge gaps, such as the ill-defined distinction between basal and damage-induced mitophagy, which must be resolved to boost progress in this area.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14138Informations de copyright
© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
Références
Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909-950. doi:10.1152/physrev.00026.2013
Nadalutti CA, Ayala-Peña S, Santos JH. Mitochondrial DNA damage as driver of cellular outcomes. Am J Physiol Cell Physiol. 2022;322(2):C136-C150. doi:10.1152/ajpcell.00389.2021
Meyer JN, Leung MCK, Rooney JP, et al. Mitochondria as a target of environmental toxicants. Toxicol Sci. 2013;134(1):1-17. doi:10.1093/toxsci/kft102
Zimmermann A, Madreiter-Sokolowski C, Stryeck S, Abdellatif M. Targeting the mitochondria-Proteostasis Axis to delay aging. Front Cell Dev Biol. 2021;9:656201. doi:10.3389/fcell.2021.656201
Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018;28(4):R170-R185. doi:10.1016/j.cub.2018.01.004
Bakula D, Scheibye-Knudsen M. MitophAging: mitophagy in aging and disease. Front Cell Dev Biol. 2020;8:239. doi:10.3389/fcell.2020.00239
Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121-135. doi:10.1038/nrm.2017.95
Bordi M, Darji S, Sato Y, et al. mTOR hyperactivation in down syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy. Cell Death Dis. 2019;10(8):563. doi:10.1038/s41419-019-1752-5
Ko H-J, Tsai CY, Chiou SJ, et al. The phosphorylation status of Drp1-Ser637 by PKA in mitochondrial fission modulates Mitophagy via PINK1/Parkin to exert multipolar spindles assembly during mitosis. Biomolecules. 2021;11(3):424. doi:10.3390/biom11030424
Webster BR, Scott I, Traba J, Han K, Sack MN. Regulation of autophagy and mitophagy by nutrient availability and acetylation. Biochim Biophys Acta. 2014;1841(4):525-534. doi:10.1016/j.bbalip.2014.02.001
Krantz S, Kim YM, Srivastava S, et al. Mitophagy mediates metabolic reprogramming of induced pluripotent stem cells undergoing endothelial differentiation. J Biol Chem. 2021;297(6):101410. doi:10.1016/j.jbc.2021.101410
Esteban-Martínez L, Sierra-Filardi E, McGreal RS, et al. Programmed mitophagy is essential for the glycolytic switch during cell differentiation. EMBO J. 2017;36(12):1688-1706. doi:10.15252/embj.201695916
Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018;19(6):349-364. doi:10.1038/s41580-018-0003-4
Ge P, Dawson VL, Dawson TM. PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson's disease. Mol Neurodegener. 2020;15(1):20. doi:10.1186/s13024-020-00367-7
Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol. 2010;191(5):933-942. doi:10.1083/jcb.201008084
Tang MY, Vranas M, Krahn AI, Pundlik S, Trempe JF, Fon EA. Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation. Nat Commun. 2017;8:14697. doi:10.1038/ncomms14697
Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524(7565):309-314. doi:10.1038/nature14893
Zhuang N, Li L, Chen S, Wang T. PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control. Cell Death Dis. 2016;7(12):e2501. doi:10.1038/cddis.2016.396
Gladkova C, Maslen SL, Skehel JM, Komander D. Mechanism of parkin activation by PINK1. Nature. 2018;559(7714):410-414. doi:10.1038/s41586-018-0224-x
Kazlauskaite A, Kondapalli C, Gourlay R, et al. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J. 2014;460(1):127-139. doi:10.1042/BJ20140334
Shiba-Fukushima K, Arano T, Matsumoto G, et al. Phosphorylation of mitochondrial Polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. 2014;10(12):e1004861. doi:10.1371/journal.pgen.1004861
Wong YC, Holzbaur ELF. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A. 2014;111(42):E4439-E4448. doi:10.1073/pnas.1405752111
Strappazzon F, Nazio F, Corrado M, et al. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 2015;22(3):419-432. doi:10.1038/cdd.2014.139
Verlhac P, Grégoire IP, Azocar O, et al. Autophagy receptor NDP52 regulates pathogen-containing autophagosome maturation. Cell Host Microbe. 2015;17(4):515-525. doi:10.1016/j.chom.2015.02.008
Nguyen TN, Padman BS, Usher J, Oorschot V, Ramm G, Lazarou M. Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J Cell Biol. 2016;215(6):857-874. doi:10.1083/jcb.201607039
Yamano K, Kikuchi R, Kojima W, et al. Critical role of mitochondrial ubiquitination and the OPTN-ATG9A axis in mitophagy. J Cell Biol. 2020;219(9):e201912144. doi:10.1083/jcb.201912144
Sentelle RD, Senkal CE, Jiang W, et al. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol. 2012;8(10):831-838. doi:10.1038/nchembio.1059
Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6(8):1090-1106. doi:10.4161/auto.6.8.13426
Okatsu K, Saisho K, Shimanuki M, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells. 2010;15(8):887-900. doi:10.1111/j.1365-2443.2010.01426.x
Diwan A, Matkovich SJ, Yuan Q, et al. Endoplasmic reticulum-mitochondria crosstalk in NIX-mediated murine cell death. J Clin Invest. 2008;119:JCI36445. doi:10.1172/JCI36445
Zhang J, Loyd MR, Randall MS, Waddell MB, Kriwacki RW, Ney PA. A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. Autophagy. 2012;8(9):1325-1332. doi:10.4161/auto.20764
Diwan A, Koesters AG, Odley AM, et al. Unrestrained erythroblast development in nix−/− mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci. 2007;104(16):6794-6799. doi:10.1073/pnas.0610666104
Schweers RL, Zhang J, Randall MS, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A. 2007;104(49):19500-19505. doi:10.1073/pnas.0708818104
Sandoval H, Thiagarajan P, Dasgupta SK, et al. Essential role for nix in autophagic maturation of erythroid cells. Nature. 2008;454(7201):232-235. doi:10.1038/nature07006
Marinković M, Šprung M, Novak I. Dimerization of mitophagy receptor BNIP3L/NIX is essential for recruitment of autophagic machinery. Autophagy. 2021;17(5):1232-1243. doi:10.1080/15548627.2020.1755120
Rogov VV, Suzuki H, Marinković M, et al. Phosphorylation of the mitochondrial autophagy receptor nix enhances its interaction with LC3 proteins. Sci Rep. 2017;7(1):1131. doi:10.1038/s41598-017-01258-6
da Silva Rosa SC, Martens MD, Field JT, et al. BNIP3L/nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation. Autophagy. 2021;17(9):2257-2272. doi:10.1080/15548627.2020.1821548
London E, Stratakis CA. The regulation of PKA signaling in obesity and in the maintenance of metabolic health. Pharmacol Ther. 2022;237:108113. doi:10.1016/j.pharmthera.2022.108113
Hamacher-Brady A, Brady NR, Logue SE, et al. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ. 2007;14(1):146-157. doi:10.1038/sj.cdd.4401936
Tang C, Han H, Liu Z, et al. Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury. Cell Death Dis. 2019;10(9):677. doi:10.1038/s41419-019-1899-0
Poole LP, Bock-Hughes A, Berardi DE, Macleod KF. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci Rep. 2021;11(1):20526. doi:10.1038/s41598-021-00170-4
McWilliams TG, Prescott AR, Montava-Garriga L, et al. Basal Mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab. 2018;27(2):439-449.e5. doi:10.1016/j.cmet.2017.12.008
Landes T, Emorine LJ, Courilleau D, Rojo M, Belenguer P, Arnauné-Pelloquin L. The BH3-only Bnip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms. EMBO Rep. 2010;11(6):459-465. doi:10.1038/embor.2010.50
Ajoolabady A, Aslkhodapasandhokmabad H, Aghanejad A, Zhang Y, Ren J. Mitophagy receptors and mediators: therapeutic targets in the management of cardiovascular ageing. Ageing Res Rev. 2020;62:101129. doi:10.1016/j.arr.2020.101129
Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2):177-185. doi:10.1038/ncb2422
Rafelski SM. Mitochondrial network morphology: building an integrative, geometrical view. BMC Biol. 2013;11(1):71. doi:10.1186/1741-7007-11-71
Liu YJ, McIntyre RL, Janssens GE, Houtkooper RH. Mitochondrial fission and fusion: a dynamic role in aging and potential target for age-related disease. Mech Ageing Dev. 2020;186:111212. doi:10.1016/j.mad.2020.111212
Graef M. A dividing matter: Drp1/Dnm1-independent mitophagy. J Cell Biol. 2016;215(5):599-601. doi:10.1083/jcb.201611079
Twig G, Elorza A, Molina AJA, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27(2):433-446. doi:10.1038/sj.emboj.7601963
Kleele T, Rey T, Winter J, et al. Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature. 2021;593(7859):435-439. doi:10.1038/s41586-021-03510-6
Yamashita S-I, Jin X, Furukawa K, et al. Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy. J Cell Biol. 2016;215(5):649-665. doi:10.1083/jcb.201605093
Lee Y, Lee HY, Hanna RA, Gustafsson ÅB. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;301(5):H1924-H1931. doi:10.1152/ajpheart.00368.2011
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021;17(1):1-382. doi:10.1080/15548627.2020.1797280
Lee JJ, Sanchez-Martinez A, Zarate AM, et al. Basal mitophagy is widespread in drosophila but minimally affected by loss of Pink1 or parkin. J Cell Biol. 2018;217(5):1613-1622. doi:10.1083/jcb.201801044
Cornelissen T, Vilain S, Vints K, Gounko N, Verstreken P, Vandenberghe W. Deficiency of parkin and PINK1 impairs age-dependent mitophagy in drosophila. Elife. 2018;7:e35878. doi:10.7554/eLife.35878
Costello MJ, Brennan LA, Basu S, et al. Autophagy and mitophagy participate in ocular lens organelle degradation. Exp Eye Res. 2013;116:141-150. doi:10.1016/j.exer.2013.08.017
McWilliams TG, Prescott AR, Villarejo-Zori B, Ball G, Boya P, Ganley IG. A comparative map of macroautophagy and mitophagy in the vertebrate eye. Autophagy. 2019;15(7):1296-1308. doi:10.1080/15548627.2019.1580509
Morishita H, Eguchi T, Tsukamoto S, et al. Organelle degradation in the lens by PLAAT phospholipases. Nature. 2021;592(7855):634-638. doi:10.1038/s41586-021-03439-w
Zhang W, Ma Q, Siraj S, et al. Nix-mediated mitophagy regulates platelet activation and life span. Blood Adv. 2019;3(15):2342-2354. doi:10.1182/bloodadvances.2019032334
Rodriguez-Enriquez S, Kai Y, Maldonado E, Currin RT, Lemasters JJ. Roles of mitophagy and the mitochondrial permeability transition in remodeling of cultured rat hepatocytes. Autophagy. 2009;5(8):1099-1106. doi:10.4161/auto.5.8.9825
Elmore SP, Qian T, Grissom SF, Lemasters JJ. The mitochondrial permeability transition initiates autophagy in rat hepatocytes. FASEB J. 2001;15(12):2286-2287. doi:10.1096/fj.01-0206fje
Guo X, Sun XY, Hu D, et al. VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington's disease. Nat Commun. 2016;7(1):12646. doi:10.1038/ncomms12646
Kim NC, Tresse E, Kolaitis RM, et al. VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations. Neuron. 2013;78(1):65-80. doi:10.1016/j.neuron.2013.02.029
Gureev AP, Shaforostova EA, Popov VN. Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1α signaling pathways. Front Genet. 2019;10:435. doi:10.3389/fgene.2019.00435
Nezich CL, Wang C, Fogel AI, Youle RJ. MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5. J Cell Biol. 2015;210(3):435-450. doi:10.1083/jcb.201501002
Settembre C, de Cegli R, Mansueto G, et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol. 2013;15(6):647-658. doi:10.1038/ncb2718
Evans TD, Zhang X, Jeong SJ, et al. TFEB drives PGC-1α expression in adipocytes to protect against diet-induced metabolic dysfunction. Sci Signal. 2019;12(606):eaau2281. doi:10.1126/scisignal.aau2281
Lynch MR, Tran MT, Ralto KM, et al. TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance. JCI Insight. 2019;4(8):e126749. doi:10.1172/jci.insight.126749
Palikaras K, Lionaki E, Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015;521(7553):525-528. doi:10.1038/nature14300
Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin a induces mitophagy and prolongs lifespan in C. Elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879-888. doi:10.1038/nm.4132
Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428-1438. doi:10.1038/nm.4222
Messerer J, Wrede C, Schipke J, et al. Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice. J Anat. 2021;242:91-101. doi:10.1111/joa.13618
Liu L, Li Y, Wang J, et al. Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis. EMBO Rep. 2021;22(3):e50629. doi:10.15252/embr.202050629
Vainshtein A, Desjardins EMA, Armani A, Sandri M, Hood DA. PGC-1α modulates denervation-induced mitophagy in skeletal muscle. Skelet Muscle. 2015;5(1):9. doi:10.1186/s13395-015-0033-y
Kim M, Shen M, Ngoy S, Karamanlidis G, Liao R, Tian R. AMPK isoform expression in the normal and failing hearts. J Mol Cell Cardiol. 2012;52(5):1066-1073. doi:10.1016/j.yjmcc.2012.01.016
Wang B, Nie J, Wu L, et al. AMPKα2 protects against the development of heart failure by enhancing Mitophagy via PINK1 phosphorylation. Circ Res. 2018;122(5):712-729. doi:10.1161/CIRCRESAHA.117.312317
Kaminaris A, Kobayashi S, McStay G, Liang Q. AMPK negatively regulates mitophagy in the heart. FASEB J. 2017;31(S1):634.1. doi:10.1096/fasebj.31.1_supplement.634.1
Liang J, Xu ZX, Ding Z, et al. Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance. Nat Commun. 2015;6(1):7926. doi:10.1038/ncomms8926
Song SB, Hwang E. A rise in ATP, ROS, and mitochondrial content upon glucose withdrawal correlates with a dysregulated mitochondria turnover mediated by the activation of the protein deacetylase SIRT1. Cell. 2018;8(1):11. doi:10.3390/cells8010011
London E, Bloyd M, Stratakis CA. PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies. J Endocrinol. 2020;246(3):R51-R64. doi:10.1530/JOE-20-0035
Yang H, Yang L. Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. J Mol Endocrinol. 2016;57(2):R93-R108. doi:10.1530/JME-15-0316
Ould Amer Y, Hebert-Chatelain E. Mitochondrial cAMP-PKA signaling: what do we really know? Biochim Biophys Acta Bioenerg. 2018;1859(9):868-877. doi:10.1016/j.bbabio.2018.04.005
Akabane S, Uno M, Tani N, et al. PKA regulates PINK1 stability and Parkin recruitment to damaged mitochondria through phosphorylation of MIC60. Mol Cell. 2016;62(3):371-384. doi:10.1016/j.molcel.2016.03.037
Lobo MJ, Reverte-Salisa L, Chao YC, et al. Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy. Commun Biol. 2020;3(1):596. doi:10.1038/s42003-020-01311-7
Grisan F, Iannucci LF, Surdo NC, et al. PKA compartmentalization links cAMP signaling and autophagy. Cell Death Differ. 2021;28(8):2436-2449. doi:10.1038/s41418-021-00761-8
Thomas A, Marek-Iannucci S, Tucker KC, Andres AM, Gottlieb RA. Decrease of cardiac Parkin protein in obese mice. Front Cardiovasc Med. 2019;6:191. doi:10.3389/fcvm.2019.00191
Vos M, Dulovic-Mahlow M, Mandik F, et al. Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency. Proc Natl Acad Sci U S A. 2021;118(43):e2025347118. doi:10.1073/pnas.2025347118
Chu CT, Ji J, Dagda RK, et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol. 2013;15(10):1197-1205. doi:10.1038/ncb2837
Glick D, Zhang W, Beaton M, et al. BNip3 regulates mitochondrial function and lipid metabolism in the liver. Mol Cell Biol. 2012;32(13):2570-2584. doi:10.1128/MCB.00167-12
Shimobayashi M, Hall MN. Multiple amino acid sensing inputs to mTORC1. Cell Res. 2016;26(1):7-20. doi:10.1038/cr.2015.146
Wang S, Tsun ZY, Wolfson RL, et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science. 2015;347(6218):188-194. doi:10.1126/science.1257132
Han JM, Jeong SJ, Park MC, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149(2):410-424. doi:10.1016/j.cell.2012.02.044
Durán RV, Oppliger W, Robitaille AM, et al. Glutaminolysis activates rag-mTORC1 signaling. Mol Cell. 2012;47(3):349-358. doi:10.1016/j.molcel.2012.05.043
Durán RV, MacKenzie ED, Boulahbel H, et al. HIF-independent role of prolyl hydroxylases in the cellular response to amino acids. Oncogene. 2013;32(38):4549-4556. doi:10.1038/onc.2012.465
Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132-141. doi:10.1038/ncb2152
Mito T, Vincent AE, Faitg J, et al. Mosaic dysfunction of mitophagy in mitochondrial muscle disease. Cell Metab. 2022;34(2):197-208.e5. doi:10.1016/j.cmet.2021.12.017
Zhang X, Sergin I, Evans TD, et al. High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy. Nat Metab. 2020;2(1):110-125. doi:10.1038/s42255-019-0162-4
Bartolomé A, García-Aguilar A, Asahara SI, et al. MTORC1 regulates both general autophagy and Mitophagy induction after oxidative phosphorylation uncoupling. Mol Cell Biol. 2017;37(23):e00441. doi:10.1128/MCB.00441-17
Desai BN, Myers BR, Schreiber SL. FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2002;99(7):4319-4324. doi:10.1073/pnas.261702698
Betz C, Stracka D, Prescianotto-Baschong C, Frieden M, Demaurex N, Hall MN. Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci U S A. 2013;110(31):12526-12534. doi:10.1073/pnas.1302455110
Melser S, Chatelain EH, Lavie J, et al. Rheb regulates Mitophagy induced by mitochondrial energetic status. Cell Metab. 2013;17(5):719-730. doi:10.1016/j.cmet.2013.03.014
Boakye YD, Groyer L, Heiss EH. An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages. Biochim Biophys Acta Gen Subj. 2018;1862(1):61-70. doi:10.1016/j.bbagen.2017.10.006
Totiger TM, Srinivasan S, Jala VR, et al. Urolithin a, a novel natural compound to target PI3K/AKT/mTOR pathway in pancreatic cancer. Mol Cancer Ther. 2019;18(2):301-311. doi:10.1158/1535-7163.MCT-18-0464
Marino G, Pietrocola F, Eisenberg T, et al. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell. 2014;53(5):710-725. doi:10.1016/j.molcel.2014.01.016
Wu W, Li K, Guo S, et al. P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system. Cell Death Discov. 2021;7(1):128. doi:10.1038/s41420-021-00513-0
Pougovkina O, te Brinke H, Ofman R, et al. Mitochondrial protein acetylation is driven by acetyl-CoA from fatty acid oxidation. Hum Mol Genet. 2014;23(13):3513-3522. doi:10.1093/hmg/ddu059
Hong SY, Ng LT, Ng LF, et al. The role of mitochondrial non-enzymatic protein acylation in ageing. PloS One. 2016;11(12):e0168752. doi:10.1371/journal.pone.0168752
Webster BR, Scott I, Han K, et al. Restricted mitochondrial protein acetylation initiates mitochondrial autophagy. J Cell Sci. 2013;126:4843-4849. doi:10.1242/jcs.131300
Stoner MW, Thapa D, Zhang M, et al. α-Lipoic acid promotes α-tubulin hyperacetylation and blocks the turnover of mitochondria through mitophagy. Biochem J. 2016;473(12):1821-1830. doi:10.1042/BCJ20160281
Tseng AHH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013;63:222-234. doi:10.1016/j.freeradbiomed.2013.05.002
Hunter T. The age of crosstalk: phosphorylation, ubiquitination, and beyond. Mol Cell. 2007;28(5):730-738. doi:10.1016/j.molcel.2007.11.019
Davidson MT, Grimsrud PA, Lai L, et al. Extreme acetylation of the cardiac mitochondrial proteome does not promote heart failure. Circ Res. 2020;127(8):1094-1108. doi:10.1161/CIRCRESAHA.120.317293
Deng Y, Xie M, Li Q, et al. Targeting mitochondria-inflammation circuit by β-Hydroxybutyrate mitigates HFpEF. Circ Res. 2021;128(2):232-245. doi:10.1161/CIRCRESAHA.120.317933
Wu KKL, Long KK, Lin H, et al. The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages. Nat Commun. 2021;12(1):6637. doi:10.1038/s41467-021-26987-1
Zhong Z, Umemura A, Sanchez-Lopez E, et al. NF-κB restricts Inflammasome activation via elimination of damaged mitochondria. Cell. 2016;164(5):896-910. doi:10.1016/j.cell.2015.12.057
Zhang N-P, Liu XJ, Xie L, Shen XZ, Wu J. Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis. Lab Invest. 2019;99(6):749-763. doi:10.1038/s41374-018-0177-6
Schroeder S, Hofer SJ, Zimmermann A, et al. Dietary spermidine improves cognitive function. Cell Rep. 2021;35(2):108985. doi:10.1016/j.celrep.2021.108985
Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305-1314. doi:10.1038/ncb1975
Pietrocola F, Lachkar S, Enot DP, et al. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015;22(3):509-516. doi:10.1038/cdd.2014.215
Morselli E, Mariño G, Bennetzen MV, et al. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J Cell Biol. 2011;192(4):615-629. doi:10.1083/jcb.201008167
Zhang H, Alsaleh G, Feltham J, et al. Polyamines control eIF5A Hypusination, TFEB translation, and autophagy to reverse B cell senescence. Mol Cell. 2019;76(1):110-125.e9. doi:10.1016/j.molcel.2019.08.005
Liang Y, Piao C, Beuschel CB, et al. eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction. Cell Rep. 2021;35(2):108941. doi:10.1016/j.celrep.2021.108941
Puleston DJ, Buck MD, Klein Geltink RI, et al. Polyamines and eIF5A Hypusination modulate mitochondrial respiration and macrophage activation. Cell Metab. 2019;30(2):352-363.e8. doi:10.1016/j.cmet.2019.05.003
Qi Y, Qiu Q, Gu X, Tian Y, Zhang Y. ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts. Sci Rep. 2016;6(1):24700. doi:10.1038/srep24700
Cirotti C, Filomeni G. ATM plays antioxidant, boosting mitophagy via denitrosylation. Autophagy. 2021;17(2):590-592. doi:10.1080/15548627.2020.1860490
Holbert CE, Dunworth M, Foley JR, Dunston TT, Stewart TM, Casero RA Jr. Autophagy induction by exogenous polyamines is an artifact of bovine serum amine oxidase activity in culture serum. J Biol Chem. 2020;295(27):9061-9068. doi:10.1074/jbc.RA120.013867
Wang J, Li S, Wang J, et al. Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function. Aging. 2020;12(1):650-671. doi:10.18632/aging.102647
Affronti HC, Rowsam AM, Pellerite AJ, et al. Pharmacological polyamine catabolism upregulation with methionine salvage pathway inhibition as an effective prostate cancer therapy. Nat Commun. 2020;11(1):52. doi:10.1038/s41467-019-13950-4
Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, et al. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 2017;547(7661):109-113. doi:10.1038/nature22964
Meng L, Lu C, Wu B, et al. Taurine antagonizes macrophages M1 polarization by Mitophagy-glycolysis switch blockage via dragging SAM-PP2Ac Transmethylation. Front Immunol. 2021;12:648913. doi:10.3389/fimmu.2021.648913
Wang S-H, Zhu XL, Wang F, et al. LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity. Cell Death Dis. 2021;12(6):557. doi:10.1038/s41419-021-03821-6
Sakakibara K, Eiyama A, Suzuki SW, et al. Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling. EMBO J. 2015;34(21):2703-2719. doi:10.15252/embj.201591440
Kaur J, Goldsmith J, Tankka A, et al. Atg32-dependent mitophagy sustains spermidine and nitric oxide required for heat-stress tolerance in Saccharomyces cerevisiae. J Cell Sci. 2021;134(11):jcs253781. doi:10.1242/jcs.253781
Abdellatif M, Trummer-Herbst V, Koser F, et al. Nicotinamide for the treatment of heart failure with preserved ejection fraction. Sci Transl Med. 2021;13(580):eabd7064. doi:10.1126/scitranslmed.abd7064
Amjad S, Nisar S, Bhat AA, et al. Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Metab. 2021;49:101195. doi:10.1016/j.molmet.2021.101195
Fang EF, Hou Y, Lautrup S, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10(1):5284. doi:10.1038/s41467-019-13172-8
Jang S, Kang HT, Hwang ES. Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J Biol Chem. 2012;287(23):19304-19314. doi:10.1074/jbc.M112.363747
Liu D, Pitta M, Jiang H, et al. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging. 2013;34(6):1564-1580. doi:10.1016/j.neurobiolaging.2012.11.020
Hsu C-P, Oka S, Shao D, Hariharan N, Sadoshima J. Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circ Res. 2009;105(5):481-491. doi:10.1161/CIRCRESAHA.109.203703
Lee IH, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci. 2008;105(9):3374-3379. doi:10.1073/pnas.0712145105
Huang R, Xu Y, Wan W, et al. Deacetylation of nuclear LC3 drives autophagy initiation under starvation. Mol Cell. 2015;57(3):456-466. doi:10.1016/j.molcel.2014.12.013
Hariharan N, Maejima Y, Nakae J, Paik J, DePinho RA, Sadoshima J. Deacetylation of FoxO by Sirt1 plays an essential role in mediating starvation-induced autophagy in cardiac myocytes. Circ Res. 2010;107(12):1470-1482. doi:10.1161/CIRCRESAHA.110.227371
He J, Zhang G, Pang Q, et al. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. FEBS J. 2017;284(9):1324-1337. doi:10.1111/febs.14055
Takasaka N, Araya J, Hara H, et al. Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence. J Immunol. 2014;192(3):958-968. doi:10.4049/jimmunol.1302341
Zhang Y-J, Zhang M, Zhao X, et al. NAD+ administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux. Basic Res Cardiol. 2020;115(5):57. doi:10.1007/s00395-020-0817-z
Kang HT, Hwang ES. Nicotinamide enhances mitochondria quality through autophagy activation in human cells. Aging Cell. 2009;8(4):426-438. doi:10.1111/j.1474-9726.2009.00487.x
Song SB, Jang SY, Kang HT, et al. Modulation of mitochondrial membrane potential and ROS generation by nicotinamide in a manner independent of SIRT1 and Mitophagy. Mol Cells. 2017;40(7):503-514. doi:10.14348/molcells.2017.0081
Stekovic S, Hofer SJ, Tripolt N, et al. Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans. Cell Metab. 2020;31(4):878-881. doi:10.1016/j.cmet.2020.02.011
Voglhuber J, Ljubojevic-Holzer S, Abdellatif M, Sedej S. Targeting cardiovascular risk factors through dietary adaptations and caloric restriction Mimetics. Front Nutr. 2021;8:758058. doi:10.3389/fnut.2021.758058
Madeo F, Zimmermann A, Maiuri MC, Kroemer G. Essential role for autophagy in life span extension. J Clin Invest. 2015;125(1):85-93. doi:10.1172/JCI73946
Mehrabani S, Bagherniya M, Askari G, Read MI, Sahebkar A. The effect of fasting or calorie restriction on mitophagy induction: a literature review. J Cachexia Sarcopenia Muscle. 2020;11(6):1447-1458. doi:10.1002/jcsm.12611
Price JC, Khambatta CF, Li KW, et al. The effect of long term calorie restriction on in vivo hepatic Proteostatis: a novel combination of dynamic and quantitative proteomics. Mol Cell Proteomics. 2012;11(12):1801-1814. doi:10.1074/mcp.M112.021204
Jamart C, Naslain D, Gilson H, Francaux M. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state. Am J Physiol Endocrinol Metab. 2013;305(8):E964-E974. doi:10.1152/ajpendo.00270.2013
Islam H, Amato A, Bonafiglia JT, et al. Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle. Pflugers Arch. 2021;473(2):241-252. doi:10.1007/s00424-020-02499-7
Tarpey MD, Davy KP, McMillan RP, et al. Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal. Mol Metab. 2017;6(12):1597-1609. doi:10.1016/j.molmet.2017.10.006
Shirakabe A, Fritzky L, Saito T, et al. Evaluating mitochondrial autophagy in the mouse heart. J Mol Cell Cardiol. 2016;92:134-139. doi:10.1016/j.yjmcc.2016.02.007
Zhao Y, Zhu Q, Song W, Gao B. Exercise training and dietary restriction affect PINK1/Parkin and Bnip3/nix-mediated cardiac mitophagy in mice. Gen Physiol Biophys. 2018;37(6):657-666. doi:10.4149/gpb_2018020
Sun N, Yun J, Liu J, et al. Measuring in vivo Mitophagy. Mol Cell. 2015;60(4):685-696. doi:10.1016/j.molcel.2015.10.009
Schwalm C, Jamart C, Benoit N, et al. Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J. 2015;29(8):3515-3526. doi:10.1096/fj.14-267187
Schwalm C, Deldicque L, Francaux M. Lack of activation of Mitophagy during endurance exercise in human. Med Sci Sports Exerc. 2017;49(8):1552-1561. doi:10.1249/MSS.0000000000001256
Zhang H, Menzies KJ, Auwerx J. The role of mitochondria in stem cell fate and aging. Development. 2018;145(8):dev143420. doi:10.1242/dev.143420
Ma T, Li J, Xu Y, et al. Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming. Nat Cell Biol. 2015;17(11):1379-1387. doi:10.1038/ncb3256
Vazquez-Martin A, den Haute CV, Cufí S, et al. Mitophagy-driven mitochondrial rejuvenation regulates stem cell fate. Aging. 2016;8(7):1330-1349. doi:10.18632/aging.100976
Zhao J-F, Rodger CE, Allen GFG, Weidlich S, Ganley IG. HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation. Cell Stress. 2020;4(5):99-113. doi:10.15698/cst2020.05.220
Esteban-Martínez L, Boya P. BNIP3L/NIX-dependent mitophagy regulates cell differentiation via metabolic reprogramming. Autophagy. 2018;14(5):915-917. doi:10.1080/15548627.2017.1332567
García-Prat L, Martínez-Vicente M, Perdiguero E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016;529(7584):37-42. doi:10.1038/nature16187
Zhao Y, Zhou L, Li H, et al. Nuclear-encoded lncRNA MALAT1 epigenetically controls metabolic reprogramming in HCC cells through the Mitophagy pathway. Mol Ther Nucleic Acids. 2021;23:264-276. doi:10.1016/j.omtn.2020.09.040
Yin K, Lee J, Liu Z, et al. Mitophagy protein PINK1 suppresses colon tumor growth by metabolic reprogramming via p53 activation and reducing acetyl-CoA production. Cell Death Differ. 2021;28(8):2421-2435. doi:10.1038/s41418-021-00760-9
Wang L, Xu X, Jiang C, et al. mTORC1-PGC1 axis regulates mitochondrial remodeling during reprogramming. FEBS J. 2020;287(1):108-121. doi:10.1111/febs.15024
Abdellatif M, Rainer PP, Sedej S, Kroemer G. Hallmarks of cardiovascular ageing. Nat Rev Cardiol. 2023;20:754-777. doi:10.1038/s41569-023-00881-3
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243-278. doi:10.1016/j.cell.2022.11.001
Tufi R, Gandhi S, de Castro IP, et al. Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson's disease. Nat Cell Biol. 2014;16(2):157-166. doi:10.1038/ncb2901
Lehmann S, Loh SHY, Martins LM. Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease. Biol Open. 2016;6:141-147. doi:10.1242/bio.022186
Zhou B, Kreuzer J, Kumsta C, et al. Mitochondrial permeability uncouples elevated autophagy and lifespan extension. Cell. 2019;177(2):299-314.e16. doi:10.1016/j.cell.2019.02.013