Open AccessMitochondrial quality control, promoted by PGC ‐1 α , is dysregulated by Western diet‐induced obesity and partially restored by moderate physical activity in mice
Author(s) -
Greene Nicholas P.,
Lee David E.,
Brown Jacob L.,
Rosa Megan E.,
Brown Lemuel A.,
Perry Richard A.,
Henry Jordyn N.,
Washington Tyrone A.
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12470
Subject(s) - mitophagy , mfn2 , mitochondrial fusion , mitochondrial biogenesis , autophagy , mitochondrion , mitochondrial fission , microbiology and biotechnology , mfn1 , mitochondrial permeability transition pore , pink1 , biology , dnaja3 , chemistry , mitochondrial dna , biochemistry , programmed cell death , apoptosis , gene
Skeletal muscle mitochondrial degeneration is a hallmark of insulin resistance/obesity marked by lost function, enhanced ROS emission, and altered morphology which may be ameliorated by physical activity ( PA ). However, no prior report has examined mitochondrial quality control regulation throughout biogenesis, fusion/fission dynamics, autophagy, and mitochondrial permeability transition pore ( MPTP ) in obesity. Therefore, we determined how each process is impacted by Western diet ( WD )‐induced obesity and whether voluntary PA may alleviate derangements in mitochondrial quality control mechanisms. Despite greater mitochondrial content following WD ( COX ‐ IV and Cytochrome C), induction of biogenesis controllers appears impaired (failed induction of PGC ‐1 α ). Mitochondrial fusion seems diminished (reduced MFN 2, Opa1 proteins), with no significant changes in fission, suggesting a shift in balance of dynamics regulation favoring fission. Autophagy flux was promoted in WD (reduced p62, increased LC 3 II :I ratio); however, mitophagy marker BNIP 3 is reduced in WD which may indicate reduced mitophagy despite enhanced total autophagy flux. MPTP regulator Ant mRNA is reduced by WD . Few processes were impacted by physical activity. Finally, mitochondrial quality control processes are partially promoted by PGC ‐1 α , as PGC ‐1 α transgenic mice display elevated mitochondrial biogenesis and autophagy flux. Additionally, these mice exhibit elevated Mfn1 and Opa1 mRNA , with no change in protein content suggesting these factors are transcriptionally promoted by PGC ‐1 α overexpression. These data demonstrate dysfunctions across mitochondrial quality control in obesity and that PGC ‐1 α is sufficient to promote multiple, but not necessarily all, aspects of mitochondrial quality control. Mitochondrial quality control may therefore be an opportune target to therapeutically treat metabolic disease.