MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes


Journal article


Chunyan Wu, Tongtong Wang, Adhideb Ghosh, Fen Long, A. K. Sharma, Tina Dahlby, Falko Noé, I. Severi, Georgia Colleluori, Saverio Cinti, Antonio Giordano, Lianggong Ding, Radhika Khandelwal, S. Kostidis, M. Giera, L. Balazova, V. Gardeux, Laith Abu-Nawwas, Bart Deplancke, Sabita Chourasia, Sandra Kleiner, Bradford Hamilton, J. M. A. Alcántara, J. Ruiz, Matthias Blüher, Anton Pekcec, Miroslav Baláž, Atan Gross, Heike Neubauer, Christian Wolfrum
Nature Communications, 2025

Semantic Scholar DOI PubMedCentral PubMed
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APA   Click to copy
Wu, C., Wang, T., Ghosh, A., Long, F., Sharma, A. K., Dahlby, T., … Wolfrum, C. (2025). MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes. Nature Communications.


Chicago/Turabian   Click to copy
Wu, Chunyan, Tongtong Wang, Adhideb Ghosh, Fen Long, A. K. Sharma, Tina Dahlby, Falko Noé, et al. “MTCH2 Modulates CPT1 Activity to Regulate Lipid Metabolism of Adipocytes.” Nature Communications (2025).


MLA   Click to copy
Wu, Chunyan, et al. “MTCH2 Modulates CPT1 Activity to Regulate Lipid Metabolism of Adipocytes.” Nature Communications, 2025.


BibTeX   Click to copy

@article{chunyan2025a,
  title = {MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes},
  year = {2025},
  journal = {Nature Communications},
  author = {Wu, Chunyan and Wang, Tongtong and Ghosh, Adhideb and Long, Fen and Sharma, A. K. and Dahlby, Tina and Noé, Falko and Severi, I. and Colleluori, Georgia and Cinti, Saverio and Giordano, Antonio and Ding, Lianggong and Khandelwal, Radhika and Kostidis, S. and Giera, M. and Balazova, L. and Gardeux, V. and Abu-Nawwas, Laith and Deplancke, Bart and Chourasia, Sabita and Kleiner, Sandra and Hamilton, Bradford and Alcántara, J. M. A. and Ruiz, J. and Blüher, Matthias and Pekcec, Anton and Baláž, Miroslav and Gross, Atan and Neubauer, Heike and Wolfrum, Christian}
}

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.