THE ROLE OF PARKIN DURING ACUTE EXERCISE-INDUCED MITOPHAGY
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C.C.W. Chen1 and D.A. Hood1
Muscle Health Research Centre, School of Kinesiology and Health Science, York University,
Toronto, Canada, M3J 1P3
Autophagy is a dynamic physiological process involved in maintaining homeostasis through
delivery of long-lived proteins and organelles to acidic lysosomes for degradation. When cellular
energetic demands are increased, autophagy is upregulated for cellular maintenance.
Mitochondria that are no longer able to sustain the energy requirements of a cell are degraded
through a selective autophagic process termed mitophagy. There are numerous cellular proteins
which are involved in mitophagy but current research suggests that Parkin, an ubiquitin ligase, is
among the key players in this process. A considerable amount of research has focused on Parkin
and its role in neuronal mitophagy, but little is known about its contribution to muscle
mitophagy. To evaluate mitophagic signaling in muscle, Parkin deficient (KO) and wild-type
(WT) mice were designated to three groups: control, acute exercise, or acute exercise and 2
hours of recovery. Immediately following exercise, hindlimb muscles were extracted to isolate
intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondria. Whole muscle mass of the
quadriceps and tibialis anterior did not significantly differ between genotypes. This was
accompanied by no differences in whole muscle cytochrome c oxidase activity. IMF
mitochondrial respiration was reduced by ~50%, and was paralleled with a ~30% reduction in
mitochondrial membrane potential. However, running performance and lactate production during
exercise were similar, irrespective of the genotype of the exercised mice. Localization of
mitophagy-related protein light chain 3 (LC3) and sequestosome 1 (p62) were both significantly
elevated on isolated SS mitochondria in the absence of Parkin following acute exercise,
suggesting enhanced mitophagic flux. Furthermore, global mitochondrial ubiquitination
increased following exercise in both Parkin KO and WT runners. Our findings suggest that other
compensatory ubiquitination and mitophagy-related receptors are induced to preserve mitophagy
flux during exercise. Supported by NSERC.
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