| First Author | Katsouda A | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 7 | PubMed ID | 35616614 |
| Mgi Jnum | J:331485 | Mgi Id | MGI:7388089 |
| Doi | 10.1084/jem.20211894 | Citation | Katsouda A, et al. (2022) MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity. J Exp Med 219(7) |
| abstractText | 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 HIF1alpha, 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. |
