Back to Search Start Over

Site-1 protease inhibits mitochondrial respiration by controlling the TGF-β target gene Mss51.

Authors :
Mousa, Muhammad G.
Vuppaladhadiam, Lahari
Kelly, Meredith O.
Pietka, Terri
Ek, Shelby
Shen, Karen C.
Meyer, Gretchen A.
Finck, Brian N.
Brookheart, Rita T.
Source :
Cell Reports; Apr2023, Vol. 42 Issue 4, pN.PAG-N.PAG, 1p
Publication Year :
2023

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)-β1 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-β signaling and S1P function. [Display omitted] • Skeletal-muscle-specific S1P knockout mice have increased muscle mass • S1P negatively regulates mitochondrial respiration by increasing Mss51 expression • TGF-β1-driven Mss51 expression is controlled by S1P Mousa et al. show that site-1 protease (S1P) negatively regulates skeletal muscle mass and mitochondrial respiration. S1P inhibits respiration via its positive regulation of Mss51 expression. S1P depletion partially impairs TGF-β1-dependent Mss51 expression, implicating S1P in TGF-β1 signaling. These findings expand our understanding of the multi-faceted control of mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
26391856
Volume :
42
Issue :
4
Database :
Complementary Index
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
163292515
Full Text :
https://doi.org/10.1016/j.celrep.2023.112336