Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila

Tai Ting Lee, Po Lin Chen, Matthew P. Su, Jian Chiuan Li, Yi Wen Chang, Rei Wen Liu, Hsueh Fen Juan, Jinn Moon Yang, Shih Peng Chan, Yu Chen Tsai, Sophia von Stockum, Elena Ziviani, Azusa Kamikouchi, Horng Dar Wang, Chun Hong Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere13379
JournalAging Cell
Volume20
Issue number6
DOIs
Publication statusPublished - 2021 Jun
Externally publishedYes

Keywords

  • aging
  • Drosophila melanogaster
  • Fis1
  • mitochondria

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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