A Mitochondrial Protein May Influence How Cells Burn or Store Fuel

Key Takeaways

Researchers identified MTCH2, also called “Mitch,” as a protein involved in mitochondrial structure, cellular energy demand, and fat-cell development.
Removing MTCH2 increased fuel use in cultured human cells, including use of fatty acids, carbohydrates, and amino acids.
In mouse precursor cells, removing MTCH2 sharply reduced the cells’ ability to mature into fat-storing cells.
In genetically modified mice, lowering MTCH2 activity in muscle or fat tissue increased energy expenditure and limited fat gain under certain diet conditions.
These findings do not show that blocking MTCH2 is safe, effective, or appropriate for people.

A Mitochondrial Switch

Mitochondria constantly fuse and divide as cells adjust their energy needs. MTCH2 helps support mitochondrial fusion; when it was removed, mitochondrial networks became more fragmented and cells appeared to need more fuel to meet their energy demands.

In lab-grown human cells, this change was linked to higher cellular respiration and greater use of several nutrient types, including fatty acids. That is a cellular observation—not evidence of a human intervention.

Fat-Cell Development

The team also examined immature mouse-derived cells that can develop into fat-storing cells. Without MTCH2, far fewer of those precursor cells completed the transition, and they accumulated fewer lipid droplets.

A later study connected MTCH2 to CPT1, a key regulator of fatty-acid entry into mitochondria. Removing MTCH2 altered that control point and increased fatty-acid use in experimental systems.

What It Means

The work suggests MTCH2 helps determine whether cells direct available fuel toward energy production, cell growth, or storage. It is a useful research lead for understanding metabolism, but not a ready-made strategy for changing body composition.

MTCH2 has roles beyond fuel handling, including mitochondrial regulation and cell-survival pathways. Any future attempt to target it would need to show tissue specificity, safety, and durable benefits in human trials.

References:

Sabita Chourasia, Christopher Petucci, Clarissa Shoffler, Dina Abbasian, Hu Wang, Xianlin Han, Ehud Sivan, Alexander Brandis, Tevie Mehlman, Sergey Malitsky, Maxim Itkin, Ayala Sharp, Ron Rotkopf, Bareket Dassa, Limor Regev, Yehudit Zaltsman, Atan Gross. MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis. The EMBO Journal, 2025; 44 (4) DOI: 10.1038/s44318-024-00335-7
Chunyan Wu, Tongtong Wang, 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, Martin Giera, 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. MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes. Nature Communications, 2025; 16 (1) DOI: 10.1038/s41467-025-63880-7