biostudies-literatureKatsouda AHellenic Institute for the Study of SepsisSwiss National Science FoundationBritish Heart FoundationDeutsche ForschungsgemeinschaftHellenic Foundation for Research and InnovationCardio-Pulmonary InstituteHellenic State Scholarship Foundation IKY-Siemens Research Projects of ExcellenceEuropean Regional Development Funde20211894https://www.ebi.ac.uk/biostudies/studies/S-EPMC9143789biostudies-literatureUnknown219(7)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/TOThe Journal of experimental medicineMPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity.PMC914378911/3056EXC 2026CRC1366/1TG/19/2/34831CH/F/21/9000931003A_179434179434RG/F/21/110040Zuhra KHavaki SPapapetropoulos ABibli SIAkoumianakis IKatsouda ANagahara NDionellis VSAntoniades CGorgoulis VGKaraliota SSzabo CThanos DFleming IValakos DfalseMPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity.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/TO2022-01-01T00:00:00Z2022 Jul2026-05-09T16:21:19.538Z2025-02-19T03:23:34.828ZS-EPMC91437893561661410.1084/jem.20211894