MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes
Abstract
Abstract Metabolic disorders, including obesity and metabolic-associated steatohepatitis, arise from a chronic energy surplus. Thus, enhancing energy dissipation through increased respiration holds significant therapeutic potential for metabolic disorders. Through a comprehensive analysis of human and murine adipose tissues, along with a functional screen, we identify mitochondrial carrier homolog 2, a mitochondrial outer membrane protein, as a pivotal regulator of mitochondrial metabolism. Intriguingly, its expression in adipose tissue is a strong determinant of obesity in humans. Adipocyte-specific ablation of mitochondrial carrier homolog 2 improves mitochondrial function and whole-body energy expenditure, independent of uncoupling protein 1. Furthermore, mitochondrial carrier homolog 2 regulates mitochondrial influx of free fatty acids by modulating the sensitivity of carnitine palmitoyltransferase 1 to malonyl-CoA through direct physical interaction, leading to enhanced energy expenditure in adipocytes/adipose tissue. Here we show mitochondrial carrier homolog 2 functions as a negative regulator of energy metabolism in adipocytes and represents a potential target for treating obesity and related metabolic disorders.
Article Details
Authors (30)
Chunyan Wu
Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, Department of Chemistry
Tongtong Wang
School of Chemical Science and Engineering, Tongji University, 1239 Siping Rd, Shanghai, 200092, China
Adhideb Ghosh
Fen Long
Anand Kumar Sharma
Tina Dahlby
Falko Noé
Ilenia Severi
Georgia Colleluori
Saverio Cinti
Antonio Giordano
Lianggong Ding
Radhika Khandelwal
Sarantos Kostidis
Center for Proteomics and Metabolomics, Leiden University Medical Center
Martin Giera
Center for Proteomics and Metabolomics, Leiden University Medical Center
Lucia Balazova
Vincent Gardeux
Laith Abu-Nawwas
Bart Deplancke
Sabita Chourasia
Sandra Kleiner
Bradford S. Hamilton
Juan Manuel Alcántara Alcántara
Jonatan R. Ruiz
Matthias Blüher
Anton Pekcec
Miroslav Balaz
Atan Gross
Heike Neubauer
Christian Wolfrum