Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila
Journal
Aging cell
Journal Volume
20
Journal Issue
6
Date Issued
2021
Author(s)
Lee, Tai-Ting
Chen, Po-Lin
Su, Matthew P
Li, Jian-Chiuan
Chang, Yi-Wen
Liu, Rei-Wen
Juan, Hsueh-Fen
Yang, Jinn-Moon
Tsai, Yu-Chen
von Stockum, Sophia
Ziviani, Elena
Kamikouchi, Azusa
Wang, Horng-Dar
Chen, Chun-Hong
Abstract
Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms. By using Drosophila melanogaster as a model, we explored the effect of Fis1 mutations generated by transposon Minos-mediated integration. Mutants exhibited a higher ratio of damaged mitochondria with age as well as elevated reactive oxygen species levels compared with controls. This caused an increase in oxidative stress, resulting in large accumulations of ubiquitinated proteins, accelerated muscle function decline, and mitochondrial myopathies in young mutant flies. Ectopic expression of Fis1 isoforms was sufficient to suppress this phenotype. Loss of Fis1 led to unbalanced mitochondrial proteostasis within fly muscle, decreasing both flight capabilities and lifespan. Fis1 thus clearly plays a role in fly mitochondrial dynamics. Further investigations into the detailed function of Fis1 are necessary for exploring how mitochondrial function correlates with muscle health during aging.
Subjects
Drosophila melanogaster; Fis1; aging; mitochondria
SDGs
Other Subjects
messenger RNA; outer membrane protein; outer membrane protein fis1; reactive oxygen metabolite; superoxide; ubiquitinated protein; unclassified drug; FIS1 protein, human; membrane protein; mitochondrial protein; adult; aging; animal experiment; animal model; Article; controlled study; disorders of mitochondrial functions; Drosophila melanogaster; ectopic expression; female; flight muscle; immunofluorescence; inner membrane; male; mitochondrial dynamics; mitochondrial myopathy; mitochondrial respiration; mitochondrion; muscle function; muscle mitochondrion; muscle tissue; myopathy; nonhuman; oxidative stress; phenotype; protein degradation; protein homeostasis; real time polymerase chain reaction; skeletal muscle; thorax; transposon; yeast; animal; Drosophila melanogaster; genetics; metabolism; protein homeostasis; skeletal muscle; Aging; Animals; Drosophila melanogaster; Membrane Proteins; Mitochondrial Proteins; Muscle, Skeletal; Proteostasis
Type
journal article