| First Author | Li ME | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 3412 |
| PubMed ID | 31363081 | Mgi Jnum | J:280932 |
| Mgi Id | MGI:6362077 | Doi | 10.1038/s41467-019-11265-y |
| Citation | Li ME, et al. (2019) Role of p110a subunit of PI3-kinase in skeletal muscle mitochondrial homeostasis and metabolism. Nat Commun 10(1):3412 |
| abstractText | Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes. To determine the relationship between these abnormalities, we created mice with muscle-specific knockout of the p110alpha or p110beta catalytic subunits of PI3K. We find that mice with muscle-specific knockout of p110alpha, but not p110beta, display impaired insulin signaling and reduced muscle size due to enhanced proteasomal and autophagic activity. Despite insulin resistance and muscle atrophy, M-p110alphaKO mice show decreased serum myostatin, increased mitochondrial mass, increased mitochondrial fusion, and increased PGC1alpha expression, especially PCG1alpha2 and PCG1alpha3. This leads to enhanced mitochondrial oxidative capacity, increased muscle NADH content, and higher muscle free radical release measured in vivo using pMitoTimer reporter. Thus, p110alpha is the dominant catalytic isoform of PI3K in muscle in control of insulin sensitivity and muscle mass, and has a unique role in mitochondrial homeostasis in skeletal muscle. |
