MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity.

The Journal of experimental medicine 2022 Jul 04

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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.

Citation

Antonia Katsouda, Dimitrios Valakos, Vasilios S Dionellis, Sofia-Iris Bibli, Ioannis Akoumianakis, Sevasti Karaliota, Karim Zuhra, Ingrid Fleming, Noriyuki Nagahara, Sophia Havaki, Vassilis G Gorgoulis, Dimitris Thanos, Charalambos Antoniades, Csaba Szabo, Andreas Papapetropoulos. MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity. The Journal of experimental medicine. 2022 Jul 04;219(7)