Mousa 2023 Cell Rep
Mousa MG, Vuppaladhadiam L, Kelly MO, Pietka T, Ek S, Shen KC, Meyer GA, Finck BN, Brookheart RT (2023) Site-1 protease inhibits mitochondrial respiration by controlling the TGF-Ξ² target gene Mss51. Cell Rep 42:112336. https://doi.org/10.1016/j.celrep.2023.112336 |
Mousa Muhammad G, Vuppaladhadiam Lahari, Kelly Meredith O, Pietka Terri, Ek Shelby, Shen Karen C, Meyer Gretchen A, Finck Brian N, Brookheart Rita T (2023) Cell Rep
Abstract: The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-Ξ²1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-Ξ² signaling and S1P function. β’ Keywords: CP, Metabolism, Mss51, TGF-Ξ², Metabolism, Mitochondria, Muscle mass, Respiration, Site-1 protease, Skeletal muscle β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US MO St Louis Abumrad NA, US MO St Louis Finck BN
Labels: MiParea: Respiration, nDNA;cell genetics
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: N, NS
HRR: Oxygraph-2k
2024-04