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
doi: 10.1371/journal.pone.0225214


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:

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


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Článek vyšel v časopise


2019 Číslo 11