Τίτλος:
MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Given the clinical, economic, and societal impact of obesity, unraveling the mechanisms of adipose tissue expansion remains of fundamental significance. We previously showed that white adipose tissue (WAT) levels of 3-mercaptopyruvate sulfurtransferase (MPST), a mitochondrial cysteine-catabolizing enzyme that yields pyruvate and sulfide species, are downregulated in obesity. Here, we report that Mpst deletion results in fat accumulation in mice fed a high-fat diet (HFD) through transcriptional and metabolic maladaptation. Mpst-deficient mice on HFD exhibit increased body weight and inguinal WAT mass, reduced metabolic rate, and impaired glucose/insulin tolerance. At the molecular level, Mpst ablation activates HIF1α, downregulates subunits of the translocase of outer/inner membrane (TIM/TOM) complex, and impairs mitochondrial protein import. MPST deficiency suppresses the TCA cycle, oxidative phosphorylation, and fatty acid oxidation, enhancing lipid accumulation. Sulfide donor administration to obese mice reverses the HFD-induced changes. These findings reveal the significance of MPST for white adipose tissue biology and metabolic health and identify a potential new therapeutic target for obesity. © 2022 Katsouda et al.
Συγγραφείς:
Katsouda, A.
Valakos, D.
Dionellis, V.S.
Bibli, S.-I.
Akoumianakis, I.
Karaliota, S.
Zuhra, K.
Fleming, I.
Nagahara, N.
Havaki, S.
Gorgoulis, V.G.
Thanos, D.
Antoniades, C.
Szabo, C.
Papapetropoulos, A.
Περιοδικό:
The Journal of Experimental Medicine
Λέξεις-κλειδιά:
mitochondrial protein; sulfide; sulfurtransferase, adverse event; animal; C57BL mouse; energy metabolism; glucose intolerance; lipid diet; metabolism; mouse; obesity, Animals; Diet, High-Fat; Energy Metabolism; Glucose Intolerance; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Obesity; Sulfides; Sulfurtransferases
DOI:
10.1084/jem.20211894
