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Parkin‐Mediated Mitophagy in Skeletal Muscle with Aging and Exercise
Author(s) -
Chen Chris,
Hood David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.764.3
Subject(s) - mitophagy , parkin , skeletal muscle , mitochondrion , endocrinology , medicine , sarcopenia , autophagy , chemistry , ubiquitin ligase , pink1 , microbiology and biotechnology , ubiquitin , biology , biochemistry , apoptosis , gene , disease , parkinson's disease
In skeletal muscle, the progressive age‐related loss of muscle mass and strength is known as sarcopenia. Alterations in skeletal muscle mitochondria are considered to be a contributing factor in this process. When mitochondria are no longer able to sustain the energetic requirements of the cell, selective autophagy (mitophagy) pathways are induced to promote the clearance of damaged mitochondria. In aged muscle, dysfunctional mitochondria generate increased amounts of reactive oxygen species (ROS) and can impair quality control mechanisms that facilitate their removal. It remains unclear if mitophagy mediates this reduced response in aged muscle. Parkin is an ubiquitin ligase involved in mitophagy, but little is known about its function with aging. To evaluate mitophagic signaling in aged muscle, young (3 months) and aged (18 months) Parkin deficient (KO) mice and wild‐type (WT) animals were assigned to three groups: control, acute exercise, or acute exercise plus 2 hours of recovery. Muscle mass was reduced by 46% and 65% respectively in aged Parkin KO and WT mice when compared to their young counterparts. Furthermore, aged WT animals displayed a 25% decrease in whole muscle cytochrome c oxidase activity. This was accompanied by a 40% reduction in State 3 (active) intermyofibrillar mitochondrial respiration in aged WT animals. In response to exercise, both aged Parkin KO and WT mice exhibited ~30% declines in running performance, and increased lactic acidosis by 2.1‐ and 1.4‐fold, respectively. Interestingly, basal mitophagy flux and subsarcolemmal mitochondrial localization of LC3II, p62 and ubiquitin were augmented in both young and aged Parkin KO muscle. Acute exercise increased mitochondrial flux in young animals, but reduced flux in older muscle. Our findings indicate that the expression of mitophagy proteins and their localization to mitochondria are not decreased in aged muscle, even in the absence of Parkin. However, attenuation of exercise‐induced mitophagy in response to aging may contribute to mitochondrial accumulation and dysfunction in aged muscle. Support or Funding Information Supported by NSERC.