| First Author | Moon SH | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 6 | Pages | 106895 |
| PubMed ID | 37275531 | Mgi Jnum | J:341027 |
| Mgi Id | MGI:7489259 | Doi | 10.1016/j.isci.2023.106895 |
| Citation | Moon SH, et al. (2023) Genetic deletion of skeletal muscle iPLA(2)gamma results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism. iScience 26(6):106895 |
| abstractText | Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPLA(2)gamma in skeletal muscle mitochondria, we generated a skeletal muscle-specific calcium-independent phospholipase A(2)gamma knockout (SKMiPLA(2)gammaKO) mouse. Genetic ablation of skeletal muscle iPLA(2)gamma resulted in pronounced muscle weakness, muscle atrophy, and increased blood lactate resulting from defects in mitochondrial function impairing metabolic processing of pyruvate and resultant bioenergetic inefficiency. Mitochondria from SKMiPLA(2)gammaKO mice were dysmorphic displaying marked changes in size, shape, and interfibrillar juxtaposition. Mitochondrial respirometry demonstrated a marked impairment in respiratory efficiency with decreases in the mass and function of oxidative phosphorylation complexes and cytochrome c. Further, a pronounced decrease in mitochondrial membrane potential and remodeling of cardiolipin molecular species were prominent. Collectively, these alterations prevented body weight gain during high-fat feeding through enhanced glucose disposal without efficient capture of chemical energy thereby altering whole-body bioenergetics. |
