Open AccessLoss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila
Author(s) -
Lee TaiTing,
Chen PoLin,
Su Matthew P.,
Li JianChiuan,
Chang YiWen,
Liu ReiWen,
Juan HsuehFen,
Yang JinnMoon,
Chan ShihPeng,
Tsai YuChen,
Stockum Sophia,
Ziviani Elena,
Kamikouchi Azusa,
Wang HorngDar,
Chen ChunHong
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13379
Subject(s) - fis1 , proteostasis , biology , microbiology and biotechnology , skeletal muscle , mitochondrial fission , mitochondrion , drosophila melanogaster , mfn2 , mitochondrial fusion , genetics , mitochondrial dna , gene , endocrinology
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.