Genetic deletion of skeletal muscle iPLA₂γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism.

ABSTRACT: Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPLA₂γ in skeletal muscle mitochondria, we generated a skeletal muscle-specific calcium-independent phospholipase A₂γ knockout (SKMiPLA₂γKO) mouse. Genetic ablation of skeletal muscle iPLA₂γ 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 SKMiPLA₂γKO mice were dysmorphic displaying marked changes in size, shape, and interfibrillar juxtaposition. Mitochondrial respirometry demon

SUBMITTER: Moon SH 

PROVIDER: S-EPMC10239068 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature