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Overexpression of pink1 or parkin in indirect flight muscles promotes mitochondrial proteostasis and extends lifespan in Drosophila melanogaster


Autoři: Hongbin Si aff001;  Peng Ma aff002;  Qiying Liang aff001;  Youjie Yin aff002;  Ping Wang aff002;  Qi Zhang aff002;  Saifei Wang aff002;  Hansong Deng aff002
Působiště autorů: College of Animal Sciences and Technology, Guangxi University, Nanning, China aff001;  Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225214

Souhrn

Dysfunctional mitochondria have been implicated in aging and age-related disorders such as Parkinson’s diseases (PD). We previously showed that pink1 and parkin, two familial PD genes, function in a linear pathway to maintain mitochondrial integrity and function. Studies of mammalian cell lines also suggest that these genes regulate mitochondrial autophagy(mitophagy). Overexpressing Parkin promotes proteostasis and function of aged muscles both in fruit flies and mice, and recent studies also indicated that mitochondrial ubiquitination are accumulated in aged muscles. However, the underlying mechanisms for pink1 and parkin mediated mitophagy on longevity is not fully understood. Here, we found that mitochondrial ubiquitination increased in indirect flight muscles (IFMs) in an age-dependent manner. Overexpression of pink1 or parkin in IFMs can abolish mitochondrial ubiquitination, restore ATP level and extend lifespan, while blocking autophagy via ATG1 knock-down suppress these effects in aged IFMs. Taken together, these results show that pink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extend lifespan in an Atg1-dependent manner. Our study provides physiological evidence that mitophagy of mitochondrial ubiquitination mediated by PINK1/ Parkin is crucial for muscle function and highlights the role of mitophagy in the pathogenesis of chronic diseases like PD.

Klíčová slova:

Drosophila melanogaster – Hyperexpression techniques – Autophagic cell death – Mitochondria – Muscle functions – Ubiquitination – Muscle fibers – Muscle proteins


Zdroje

1. Chinnery PF, Samuels DC, Elson J, Turnbull DM. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? Lancet. 2002;360(9342):1323–5. Epub 2002/11/05. doi: 10.1016/S0140-6736(02)11310-9 12414225.

2. Sun N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Mol Cell. 2016;61(5):654–66. Epub 2016/03/05. doi: 10.1016/j.molcel.2016.01.028 26942670; PubMed Central PMCID: PMC4779179.

3. Tatsuta T, Langer T. Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J. 2008;27(2):306–14. Epub 2008/01/25. doi: 10.1038/sj.emboj.7601972 18216873; PubMed Central PMCID: PMC2234350.

4. Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 2013;20(1):31–42. Epub 2012/06/30. doi: 10.1038/cdd.2012.81 22743996; PubMed Central PMCID: PMC3524633.

5. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, et al. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006;441(7097):1162–6. Epub 2006/05/05. nature04779 [pii] doi: 10.1038/nature04779 16672981.

6. Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441(7097):1157–61. Epub 2006/05/05. nature04788 [pii] doi: 10.1038/nature04788 16672980.

7. Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, et al. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007;27(45):12413–8. Epub 2007/11/09. doi: 10.1523/JNEUROSCI.0719-07.2007 17989306.

8. Deng H, Dodson MW, Huang H, Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105(38):14503–8. Epub 2008/09/19. 0803998105 [pii] doi: 10.1073/pnas.0803998105 18799731; PubMed Central PMCID: PMC2567186.

9. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8(1):e1000298. Epub 2010/02/04. doi: 10.1371/journal.pbio.1000298 20126261; PubMed Central PMCID: PMC2811155.

10. 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):1090–106. Epub 2010/10/05. doi: 10.4161/auto.6.8.13426 20890124; PubMed Central PMCID: PMC3359490.

11. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524(7565):309–14. Epub 2015/08/13. doi: 10.1038/nature14893 26266977; PubMed Central PMCID: PMC5018156.

12. Demontis F, Perrimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010;143(5):813–25. Epub 2010/11/30. doi: 10.1016/j.cell.2010.10.007 21111239; PubMed Central PMCID: PMC3066043.

13. Rana A, Rera M, Walker DW. Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A. 2013;110(21):8638–43. Epub 2013/05/08. doi: 10.1073/pnas.1216197110 23650379; PubMed Central PMCID: PMC3666724.

14. Leduc-Gaudet JP, Reynaud O, Hussain SN, Gouspillou G. Parkin overexpression protects from ageing-related loss of muscle mass and strength. J Physiol. 2019;597(7):1975–91. Epub 2019/01/08. doi: 10.1113/JP277157 30614532; PubMed Central PMCID: PMC6441909.

15. Rana A, Oliveira MP, Khamoui AV, Aparicio R, Rera M, Rossiter HB, et al. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster. Nat Commun. 2017;8(1):448. Epub 2017/09/08. doi: 10.1038/s41467-017-00525-4 28878259; PubMed Central PMCID: PMC5587646.

16. Aparicio R, Rana A, Walker DW. Upregulation of the Autophagy Adaptor p62/SQSTM1 Prolongs Health and Lifespan in Middle-Aged Drosophila. Cell Rep. 2019;28(4):1029–40 e5. Epub 2019/07/25. doi: 10.1016/j.celrep.2019.06.070 31340141; PubMed Central PMCID: PMC6688777.

17. Vincow ES, Merrihew G, Thomas RE, Shulman NJ, Beyer RP, MacCoss MJ, et al. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci U S A. 2013;110(16):6400–5. Epub 2013/03/20. doi: 10.1073/pnas.1221132110 23509287; PubMed Central PMCID: PMC3631677.

18. 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. Epub 2018/05/29. doi: 10.7554/eLife.35878 29809156; PubMed Central PMCID: PMC6008047.

19. Ma P, Yun J, Deng H, Guo M. Atg1 mediated autophagy suppresses tissue degeneration in pink1/parkin mutants by promoting mitochondrial fission in Drosophila. Mol Biol Cell. 2018:mbcE18040243. Epub 2018/10/26. doi: 10.1091/mbc.E18-04-0243 30354903; PubMed Central PMCID: PMC6340213.

20. Sterky FH, Lee S, Wibom R, Olson L, Larsson NG. Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo. Proc Natl Acad Sci U S A. 2011;108(31):12937–42. Epub 2011/07/20. doi: 10.1073/pnas.1103295108 21768369; PubMed Central PMCID: PMC3150929.

21. Yun J, Puri R, Yang H, Lizzio MA, Wu C, Sheng ZH, et al. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. Elife. 2014;3:e01958. Epub 2014/06/06. doi: 10.7554/eLife.01958 24898855; PubMed Central PMCID: PMC4044952.

22. Shaid S, Brandts CH, Serve H, Dikic I. Ubiquitination and selective autophagy. Cell Death Differ. 2013;20(1):21–30. Epub 2012/06/23. doi: 10.1038/cdd.2012.72 22722335; PubMed Central PMCID: PMC3524631.

23. Nezis IP, Simonsen A, Sagona AP, Finley K, Gaumer S, Contamine D, et al. Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain. J Cell Biol. 2008;180(6):1065–71. Epub 2008/03/19. doi: 10.1083/jcb.200711108 18347073; PubMed Central PMCID: PMC2290837.

24. Kraft C, Peter M, Hofmann K. Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol. 2010;12(9):836–41. Epub 2010/09/03. doi: 10.1038/ncb0910-836 20811356.

25. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol. 2010;22(2):132–9. Epub 2010/01/09. doi: 10.1016/j.ceb.2009.12.004 20056399.

26. Park J, Kim Y, Choi S, Koh H, Lee SH, Kim JM, et al. Drosophila Porin/VDAC affects mitochondrial morphology. PLoS One. 2010;5(10):e13151. Epub 2010/10/16. doi: 10.1371/journal.pone.0013151 20949033; PubMed Central PMCID: PMC2951900.

27. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1):9–14. Epub 2010/12/24. doi: 10.1038/nrm3028 21179058; PubMed Central PMCID: PMC4780047.

28. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547–64. Epub 2012/09/05. doi: 10.1515/hsz-2012-0119 22944659; PubMed Central PMCID: PMC3630798.

29. Khalil B, El Fissi N, Aouane A, Cabirol-Pol MJ, Rival T, Lievens JC. PINK1-induced mitophagy promotes neuroprotection in Huntington's disease. Cell Death Dis. 2015;6:e1617. Epub 2015/01/23. doi: 10.1038/cddis.2014.581 25611391; PubMed Central PMCID: PMC4669776.

30. Todd AM, Staveley BE. Expression of Pink1 with alpha-synuclein in the dopaminergic neurons of Drosophila leads to increases in both lifespan and healthspan. Genet Mol Res. 2012;11(2):1497–502. Epub 2012/06/02. doi: 10.4238/2012.May.21.6 22653599.


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2019 Číslo 11
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