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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\u2010order organisms. By using <jats:italic>Drosophila melanogaster<\/jats:italic> as a model, we explored the effect of Fis1 mutations generated by transposon Minos\u2010mediated 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 <jats:italic>Fis1<\/jats:italic> 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.<\/jats:p>","DOI":"10.1111\/acel.13379","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T01:40:51Z","timestamp":1622598051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Loss of <i>Fis1<\/i> impairs proteostasis during skeletal muscle aging in <i>Drosophila<\/i>"],"prefix":"10.1111","volume":"20","author":[{"given":"Tai\u2010Ting","family":"Lee","sequence":"first","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology National Health Research Institutes  Zhunan Taiwan"},{"name":"Division of Biological Science Graduate School of Science Nagoya University  Nagoya Japan"},{"name":"Institute of Biotechnology National Tsing Hua University  Hsinchu 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