Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria

References

• Wu T, Yoon H, Xiong Y, et al. Targeted protein degradation as a powerful research tool in basic biology and drug target discovery. Nat Struct Mol Biol. 2020 Jul;27(7):605–614. doi: 10.1038/s41594-020-0438-0
   PubMed Web of Science ®Google Scholar
• Samarasinghe KTG, Crews CM. Targeted protein degradation: a promise for undruggable proteins. Cell Chem Biol. 2021 Jul 15;28(7):934–951. doi: 10.1016/j.chembiol.2021.04.011
   PubMed Web of Science ®Google Scholar
• Chamberlain PP, Hamann LG. Development of targeted protein degradation therapeutics. Nat Chem Biol. 2019 Oct;15(10):937–944. doi: 10.1038/s41589-019-0362-y
   PubMed Web of Science ®Google Scholar
• Ding Y, Fei Y, Lu B. Emerging new concepts of degrader technologies. Trends Pharmacol Sci. 2020 Jul;41(7):464–474. doi: 10.1016/j.tips.2020.04.005
   PubMed Web of Science ®Google Scholar
• Alabi SB, Crews CM. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. J Biol Chem. 2021 Jan-Jun;296:100647. doi: 10.1016/j.jbc.2021.100647
   PubMed Web of Science ®Google Scholar
• Salami J, Crews CM. Waste disposal-An attractive strategy for cancer therapy. Science. 2017 Mar 17;355(6330):1163–1167. doi: 10.1126/science.aam7340
   PubMed Web of Science ®Google Scholar
• Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 2013 Sep 5;501(7465):45–51. doi: 10.1038/nature12481
   PubMed Web of Science ®Google Scholar
• Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006 Oct 19;443(7113):787–795. doi: 10.1038/nature05292
   PubMed Web of Science ®Google Scholar
• Hou YJ, Dan XL, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 2019 Oct;15(10):565–581. doi: 10.1038/s41582-019-0244-7
   PubMed Web of Science ®Google Scholar
• Boland B, Yu WH, Corti O, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2018 Sep;17(9):660–688. doi: 10.1038/nrd.2018.109
   PubMed Web of Science ®Google Scholar
• Lou G, Palikaras K, Lautrup S, et al. Mitophagy and neuroprotection. Trends Mol Med. 2020 Jan;26(1):8–20. doi: 10.1016/j.molmed.2019.07.002
   PubMed Web of Science ®Google Scholar
• Ohsumi Y. Historical landmarks of autophagy research. Cell Res. 2014 Jan;24(1):9–23. doi: 10.1038/cr.2013.169
   PubMed Web of Science ®Google Scholar
• Mizushima N. A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol. 2018 May;20(5):521–527. doi: 10.1038/s41556-018-0092-5
   PubMed Web of Science ®Google Scholar
• Feng Y, He D, Yao Z, et al. The machinery of macroautophagy. Cell Res. 2014 Jan;24(1):24–41. doi: 10.1038/cr.2013.168
   PubMed Web of Science ®Google Scholar
• Pohl C, Dikic I. Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019 Nov 15;366(6467):818–822. doi: 10.1126/science.aax3769
   PubMed Web of Science ®Google Scholar
• Lamark T, Johansen T. Mechanisms of selective autophagy. Annu Rev Cell Dev Biol. 2021 Oct 6;37(1):143–169. doi: 10.1146/annurev-cellbio-120219-035530
   PubMedGoogle Scholar
• Yu L, Chen Y, Tooze SA. Autophagy pathway: cellular and molecular mechanisms. Autophagy. 2018;14(2):207–215. doi: 10.1080/15548627.2017.1378838
   PubMed Web of Science ®Google Scholar
• Stolz A, Ernst A, Dikic I. Cargo recognition and trafficking in selective autophagy. Nat Cell Biol. 2014 Jun;16(6):495–501. doi: 10.1038/ncb2979
   PubMed Web of Science ®Google Scholar
• Gatica D, Lahiri V, Klionsky DJ. Cargo recognition and degradation by selective autophagy. Nat Cell Biol. 2018 Mar;20(3):233–242. doi: 10.1038/s41556-018-0037-z
   PubMed Web of Science ®Google Scholar
• Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019 Jan 10;176(1–2):11–42. doi: 10.1016/j.cell.2018.09.048
   PubMed Web of Science ®Google Scholar
• Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018 Jun;19(6):349–364. doi: 10.1038/s41580-018-0003-4
   PubMed Web of Science ®Google Scholar
• Takahashi D, Arimoto H. Selective autophagy as the basis of autophagy-based degraders. Cell Chem Biol. 2021 Jul 15;28(7):1061–1071. doi: 10.1016/j.chembiol.2021.05.006
   PubMed Web of Science ®Google Scholar
• Li ZY, Wang C, Wang ZY, et al. Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds. Nature. 2019 Nov 7;575:203–209. doi: 10.1038/s41586-019-1722-1
   PubMed Web of Science ®Google Scholar
• Fu Y, Chen N, Wang Z, et al. Degradation of lipid droplets by chimeric autophagy-tethering compounds. Cell Res. 2021 Sep;31(9):965–979. doi: 10.1038/s41422-021-00532-7
   PubMed Web of Science ®Google Scholar
• Takahashi D, Moriyama J, Nakamura T, et al. Autacs: cargo-specific degraders using selective autophagy. Mol Cell. 2019 Dec 5;76:797–810. doi: 10.1016/j.molcel.2019.09.009
   PubMed Web of Science ®Google Scholar
• Ji CH, Kim HY, Lee MJ, et al. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system. Nat Commun. 2022 Feb 16;13(1):1–14. doi: 10.1038/s41467-022-28520-4
   PubMed Web of Science ®Google Scholar
• Mizushima N, Kuma A, Kobayashi Y, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci. 2003 May 1;116(Pt 9):1679–1688. doi: 10.1242/jcs.00381
   PubMed Web of Science ®Google Scholar
• Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J. 2000 Nov 1;19(21):5720–5728. doi: 10.1093/emboj/19.21.5720
   PubMed Web of Science ®Google Scholar
• Huang X, Yao J, Liu L, et al. Atg8-PE protein-based in vitro biochemical approaches to autophagy studies. Autophagy. 2022 Sep;18(9):2020–2035. doi: 10.1080/15548627.2022.2025572
   PubMed Web of Science ®Google Scholar
• Ichimura Y, Kirisako T, Takao T, et al. A ubiquitin-like system mediates protein lipidation. Nature. 2000 Nov 23;408(6811):488–492. doi: 10.1038/35044114
   PubMed Web of Science ®Google Scholar
• Lystad AH, Carlsson SR, de la Ballina LR, et al. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nat Cell Biol. 2019 Mar;21(3):372–383. doi: 10.1038/s41556-019-0274-9
   PubMed Web of Science ®Google Scholar
• Dudley LJ, Cabodevilla AG, Makar AN, et al. Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy. Embo J. 2019 May 2;38(9):e100554. doi: 10.15252/embj.2018100554
   PubMed Web of Science ®Google Scholar
• Pankiv S, Clausen TH, Lamark T, et al. P62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007 Aug 17;282(33):24131–24145. doi: 10.1074/jbc.M702824200
   PubMed Web of Science ®Google Scholar
• Viret C, Rozieres A, Faure M. Novel insights into NDP52 autophagy receptor functioning. Trends Cell Biol. 2018 Apr;28(4):255–257. doi: 10.1016/j.tcb.2018.01.003
   PubMed Web of Science ®Google Scholar
• Kirkin V, Lamark T, Sou YS, et al. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009 Feb 27;33(4):505–516. doi: 10.1016/j.molcel.2009.01.020
   PubMed Web of Science ®Google Scholar
• Qiu Y, Wang J, Li H, et al. Emerging views of OPTN (optineurin) function in the autophagic process associated with disease. Autophagy. 2022 Jan;18(1):73–85. doi: 10.1080/15548627.2021.1908722
   PubMed Web of Science ®Google Scholar
• Zhang Y, Xu X, Hu MX, et al. SPATA33 is an autophagy mediator for cargo selectivity in germline mitophagy. Cell Death Differ. 2021 Mar;28(3):1076–1090. doi: 10.1038/s41418-020-00638-2
   PubMed Web of Science ®Google Scholar
• Kirkin V, Rogov VV., Rogov VV. A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell. 2019 Oct 17;76:268–285. doi: 10.1016/j.molcel.2019.09.005
   PubMed Web of Science ®Google Scholar
• Johansen T, Lamark T. Selective autophagy: ATG8 family proteins, LIR motifs and cargo receptors. J Mol Biol. 2020 Jan 3;432(1):80–103. doi: 10.1016/j.jmb.2019.07.016
   PubMed Web of Science ®Google Scholar
• Gubas A, Dikic I. A guide to the regulation of selective autophagy receptors. FEBS J. 2022 Jan;289(1):75–89. doi: 10.1111/febs.15824
   PubMed Web of Science ®Google Scholar
• Lu K, den Brave F, Jentsch S. Receptor oligomerization guides pathway choice between proteasomal and autophagic degradation. Nat Cell Biol. 2017 Jun;19(6):732–739. doi: 10.1038/ncb3531
   PubMed Web of Science ®Google Scholar
• Boada-Romero E, Letek M, Fleischer A, et al. TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. Embo J. 2013 Feb 20;32(4):566–582. doi: 10.1038/emboj.2013.8
   PubMed Web of Science ®Google Scholar
• Goode A, Butler K, Long J, et al. Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD. Autophagy. 2016 Jul 2;12(7):1094–1104. doi: 10.1080/15548627.2016.1170257
   PubMed Web of Science ®Google Scholar
• Wirth M, Zhang W, Razi M, et al. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6
   PubMedGoogle Scholar
• Barrette-Ng IH, Wu SC, Tjia WM, et al. The structure of the SBP-Tag-streptavidin complex reveals a novel helical scaffold bridging binding pockets on separate subunits. Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):879–887. doi: 10.1107/S0907444913002576
   PubMedGoogle Scholar
• Okamoto Y, Nagai Y, Fujikake N, et al. Surface plasmon resonance characterization of specific binding of polyglutamine aggregation inhibitors to the expanded polyglutamine stretch. Biochem Biophys Res Commun. 2009 Jan 16;378(3):634–639. doi: 10.1016/j.bbrc.2008.11.094
   PubMed Web of Science ®Google Scholar
• Kanaji S, Iwahashi J, Kida Y, et al. Characterization of the signal that directs TOM20 to the mitochondrial outer membrane. J Cell Bio. 2000 Oct 16;151(2):277–288. doi: 10.1083/jcb.151.2.277
   PubMed Web of Science ®Google Scholar
• Yamada T, Murata D, Adachi Y, et al. Mitochondrial stasis reveals p62-mediated ubiquitination in Parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 2018 Oct 2;28:588–604. doi: 10.1016/j.cmet.2018.06.014
   PubMed Web of Science ®Google Scholar
• Strappazzon F, Vietri-Rudan M, Campello S, et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. Embo J. 2011 Apr 6;30(7):1195–1208. doi: 10.1038/emboj.2011.49
   PubMed Web of Science ®Google Scholar
• Zhang Y, Yao Y, Qiu X, et al. Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing. Nat Immunol. 2019 Apr;20(4):433–446. doi: 10.1038/s41590-019-0324-2
   PubMed Web of Science ®Google Scholar
• Tobias IS, Newton AC. Protein scaffolds control localized protein kinase czeta activity. J Biol Chem. 2016 Jun 24;291:13809–13822. doi: 10.1074/jbc.M116.729483
   PubMedGoogle Scholar
• Krobitsch S, Lindquist S. Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1589–1594. doi: 10.1073/pnas.97.4.1589
   PubMed Web of Science ®Google Scholar
• Kim YE, Hosp F, Frottin F, et al. Soluble oligomers of polyQ-expanded huntingtin target a multiplicity of key cellular factors. Mol Cell. 2016 Sep 15;63(6):951–964. doi: 10.1016/j.molcel.2016.07.022
   PubMed Web of Science ®Google Scholar
• Szymczak AL, Workman CJ, Wang Y, et al. Correction of multi-gene deficiency in vivo using a single ‘self-cleaving’ 2A peptide-based retroviral vector. Nat Biotechnol. 2004 May;22(5):589–594. doi: 10.1038/nbt957
   PubMed Web of Science ®Google Scholar
• Boncompain G, Divoux S, Gareil N, et al. Synchronization of secretory protein traffic in populations of cells. Nat Methods. 2012 Mar 11;9(5):493–498. doi: 10.1038/nmeth.1928
   PubMed Web of Science ®Google Scholar
• Bauer PO, Goswami A, Wong HK, et al. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat Biotechnol. 2010 Mar;28(3):256–263. doi: 10.1038/nbt.1608
   PubMed Web of Science ®Google Scholar
• Kerr JS, Adriaanse BA, Greig NH, et al. Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms. Trends Neurosci. 2017 Mar;40(3):151–166. doi: 10.1016/j.tins.2017.01.002
   PubMed Web of Science ®Google Scholar
• Springer W, Kahle PJ. Regulation of PINK1-Parkin-mediated mitophagy. Autophagy. 2011 Mar;7(3):266–278. doi: 10.4161/auto.7.3.14348
   PubMed Web of Science ®Google Scholar
• Narendra D, Tanaka A, Suen DF, et al. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Bio. 2008 Dec 1;183(5):795–803. doi: 10.1083/jcb.200809125
   PubMed Web of Science ®Google Scholar
• Yang YF, Gehrke S, Imai Y, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused inactivation of Drosophila PINK1 is rescued by by Parkin. P Natl Acad Sci USA. 2006 Jul 11;103:10793–10798. doi: 10.1073/pnas.0602493103
   PubMed Web of Science ®Google Scholar
• Pickrell AM, Youle RJ. The roles of PINK1, Parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015 Jan 21;85(2):257–273. doi: 10.1016/j.neuron.2014.12.007
   PubMed Web of Science ®Google Scholar
• Chung SY, Kishinevsky S, Mazzulli JR, et al. Parkin and PINK1 patient Ipsc-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and alpha-synuclein accumulation. Stem Cell Rep. 2016 Oct 11;7:664–677. doi: 10.1016/j.stemcr.2016.08.012
   PubMed Web of Science ®Google Scholar
• van der Merwe C, van Dyk HC, Engelbrecht L, et al. Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson’s disease from mitochondrial dysfunction and cell death. Mol Neurobiol. 2017 May;54(4):2752–2762. doi: 10.1007/s12035-016-9843-0
   PubMed Web of Science ®Google Scholar
• Gandhi S, Wood-Kaczmar A, Yao Z, et al. PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell. 2009 Mar 13;33(5):627–638. doi: 10.1016/j.molcel.2009.02.013
   PubMed Web of Science ®Google Scholar
• Lutz AK, Exner N, Fett ME, et al. Loss of Parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem. 2009 Aug 21;284(34):22938–22951. doi: 10.1074/jbc.M109.035774
   PubMed Web of Science ®Google Scholar
• Ow YP, Green DR, Hao Z, et al. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008 Jul;9:532–542. doi: 10.1038/nrm2434
   PubMed Web of Science ®Google Scholar
• Kagan VE, Tyurin VA, Jiang J, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol. 2005 Sep;1(4):223–232. doi: 10.1038/nchembio727
   PubMed Web of Science ®Google Scholar
• Livingston MJ, Wang J, Zhou J, et al. Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys. Autophagy. 2019 Dec;15(12):2142–2162. doi: 10.1080/15548627.2019.1615822
   PubMed Web of Science ®Google Scholar
• Zhou B, Zhang JY, Liu XS, et al. Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis. Cell Res. 2018 Dec;28(12):1171–1185. doi: 10.1038/s41422-018-0090-y
   PubMed Web of Science ®Google Scholar
• Vargas JNS, Wang C, Bunker E, et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell. 2019 Apr 18;74(2):347–362. doi: 10.1016/j.molcel.2019.02.010
   PubMed Web of Science ®Google Scholar
• Long J, Gallagher TR, Cavey JR, et al. Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch. J Biol Chem. 2008 Feb 29;283:5427–5440. doi: 10.1074/jbc.M704973200
   PubMed Web of Science ®Google Scholar
• Sanchez-Martin P, Komatsu M. P62/SQSTM1 - steering the cell through health and disease. J Cell Sci. 2018 Nov 5;131(21):jcs222836. doi: 10.1242/jcs.222836
   PubMed Web of Science ®Google Scholar
• Lang M, Pramstaller PP, Pichler I. Crosstalk of organelles in Parkinson’s disease - MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes. Mol Neurodegener. 2022 Jul 16;17(1):50. doi: 10.1186/s13024-022-00555-7
   PubMed Web of Science ®Google Scholar
• Zhang S, Zhao J, Quan Z, et al. Mitochondria and other organelles in neural development and their potential as therapeutic targets in neurodegenerative diseases. Front Neurosci. 2022;16:853911. doi: 10.3389/fnins.2022.853911
   PubMed Web of Science ®Google Scholar
• Torggler R, Papinski D, Brach T, et al. Two independent pathways within selective autophagy converge to activate Atg1 kinase at the vacuole. Mol Cell. 2016 Oct 20;64(2):221–235. doi: 10.1016/j.molcel.2016.09.008
   PubMed Web of Science ®Google Scholar
• Yamano K, Kikuchi R, Kojima W, et al. Critical role of mitochondrial ubiquitination and the OPTN-ATG9A axis in mitophagy. J Cell Bio. 2020 Sep 7;219(9):e201912144. doi: 10.1083/jcb.201912144
   PubMed Web of Science ®Google Scholar
• Richter B, Sliter DA, Herhaus L, et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4039–4044. doi: 10.1073/pnas.1523926113
   PubMed Web of Science ®Google Scholar
• Chu TT, Gao N, Li QQ, et al. Specific knockdown of endogenous tau protein by peptide-directed ubiquitin-proteasome degradation. Cell Chem Biol. 2016 Apr 21;23(4):453–461. doi: 10.1016/j.chembiol.2016.02.016
   PubMed Web of Science ®Google Scholar
• Qu J, Ren X, Xue F, et al. Specific knockdown of alpha-synuclein by peptide-directed proteasome degradation rescued its associated neurotoxicity. Cell Chem Biol. 2020 Jun 18;27:751–762. doi: 10.1016/j.chembiol.2020.03.010
   PubMed Web of Science ®Google Scholar
• Lu M, Liu T, Jiao Q, et al. Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway. Eur J Med Chem. 2018 Feb 25;146:251–259. doi: 10.1016/j.ejmech.2018.01.063
   PubMed Web of Science ®Google Scholar
• Ludtmann MH, Angelova PR, Ninkina NN, et al. Monomeric alpha-synuclein exerts a physiological role on brain ATP synthase. J Neurosci. 2016 Oct 12;36:10510–10521. doi: 10.1523/JNEUROSCI.1659-16.2016
   PubMed Web of Science ®Google Scholar
• Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci. 2016 Jan;17:5–21. doi: 10.1038/nrn.2015.1
   PubMed Web of Science ®Google Scholar
• Vives-Bauza C, Zhou C, Huang Y, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378–383. doi: 10.1073/pnas.0911187107
   PubMed Web of Science ®Google Scholar
• Lazarou M, Jin SM, Kane LA, et al. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell. 2012 Feb 14;22(2):320–333. doi: 10.1016/j.devcel.2011.12.014
   PubMed Web of Science ®Google Scholar
• Geisler S, Holmstrom KM, Skujat D, et al. Pink1/parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010 Feb;12(2):119–131. doi: 10.1038/ncb2012
   PubMed Web of Science ®Google Scholar
• Heo JM, Ordureau A, Paulo JA, et al. The PINK1-Parkin mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol Cell. 2015 Oct 1;60(1):7–20. doi: 10.1016/j.molcel.2015.08.016
   PubMed Web of Science ®Google Scholar
• Malpartida AB, Williamson M, Narendra DP, et al. Mitochondrial dysfunction and mitophagy in Parkinson’s disease: from mechanism to therapy. Trends Biochem Sci. 2021 Apr;46(4):329–343. doi: 10.1016/j.tibs.2020.11.007
   PubMed Web of Science ®Google Scholar
• Vives-Bauza C, Przedborski S. Mitophagy: the latest problem for Parkinson’s disease. Trends Mol Med. 2011 Mar;17:158–165. doi: 10.1016/j.molmed.2010.11.002
   PubMed Web of Science ®Google Scholar