Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila
Increased dysfunctional mitochondria within skeletal muscle is correlated with many aged-related physiopathological conditions. Understanding the links between mitochondrial function and muscle proteohomeostasis is necessary to develop treatments, yet the underlying connections remain unclear. The mitochondrial outer membrane protein Fis1, a yeast fission factor, may also maintain mitochondrial morphology in metazoans. Here, we found Fis1 isoform expression increased with age. Moreover, Fis1MI10520 (MiMIC insertion mutant) showed the higher ratio of damaged mitochondria during aging. These damaged mitochondria possessed compromised inner membrane structures, generated reduced ATP concentration and showed elevated ROS levels. This caused increased oxidative stress resulting in large accumulations of ubiquitinated protein and an accelerated decline in muscle function. Our findings indicate that Fis1 is crucial for Drosophila mitochondrial homeostasis, and Fis1 mutations cause aged phenotypes in young mutant flies. Further investigation into the larger homeostatic network containing Fis1 is necessary to improve understanding of how mitochondrial function changes with age.