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

• Published in: PloS one 2019-11, Vol.14 (11), p.e0225214-e0225214
• Main Authors: Si, Hongbin, Ma, Peng, Liang, Qiying, Yin, Youjie, Wang, Ping, Zhang, Qi, Wang, Saifei, Deng, Hansong
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Age related diseases; Aging; Animal sciences; Animals; Animals, Genetically Modified; Apoptosis; Autophagy; Biology and Life Sciences; Cell death; Cell lines; Cells (Biology); Chronic diseases; Dopamine; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Flight; Fruit flies; Fruit flies (Tephritidae); Gene Expression; Genes; Genetic research; Genotype & phenotype; Humans; Insects; Kinases; Life sciences; Life span; Medicine and Health Sciences; Microscopy; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; Movement disorders; Muscle, Skeletal - metabolism; Muscles; Neurodegenerative diseases; Parkin protein; Parkinson's disease; Pathogenesis; Phagocytosis; Proteins; PTEN-induced putative kinase; Research and Analysis Methods; Ubiquitin; Ubiquitin-Protein Ligases - genetics; Ubiquitination
• ISSN: 1932-6203; 1932-6203
• 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.