TY - JOUR
TI - MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity
AU - Katsouda, A.
AU - Valakos, D.
AU - Dionellis, V.S.
AU - Bibli, S.-I.
AU - Akoumianakis, I.
AU - Karaliota, S.
AU - Zuhra, K.
AU - Fleming, I.
AU - Nagahara, N.
AU - Havaki, S.
AU - Gorgoulis, V.G.
AU - Thanos, D.
AU - Antoniades, C.
AU - Szabo, C.
AU - Papapetropoulos, A.
JO - The Journal of Experimental Medicine
PY - 2022
VL - 219
TODO - 7
SP - null
PB - NLM (Medline)
SN - 0022-1007, 1540-9538
TODO - 10.1084/jem.20211894
TODO - 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
TODO - 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.
ER -