Researchers at USC discover a tiny mitochondrial microprotein, MENTSH, that may shed light on genetic vulnerabilities in type 2 diabetes, offering potential new avenues for targeted treatments.
Researchers at the University of Southern California have identified a tiny mitochondrial microprotein that may help explain why some people are more vulnerable to type 2 diabetes, adding to a growing body of work suggesting that mitochondrial biology plays a much bigger role in metabolic disease than once thought. The protein, named MENTSH, appears to be produced from a region of mitochondrial DNA and is linked to a genetic variant that raises diabetes risk in a large health and genetics dataset.
According to a study published in Diabetes in 2024, the variant was found in analysis of health and genetic data from about 15,000 adults and appears to interfere with the protein’s starting signal, reducing MENTSH levels in some people. The same study reported that restoring the protein in cells improved insulin responsiveness, while modified versions of MENTSH helped limit weight gain in mice fed a high-fat diet.
The findings fit with earlier research showing that mitochondrial proteins are closely tied to type 2 diabetes. A 2018 analysis of skeletal muscle tissue from people with and without the disease found widespread differences in mitochondrial protein expression, including reduced activity in metabolic pathways. More recently, a 2025 University of Michigan study found misfolded proteins building up inside mitochondria in patients with type 2 diabetes, creating cellular stress and contributing to the death of insulin-producing beta cells.
Other studies have also pointed to specific mitochondrial proteins as possible therapeutic targets. Research on the outer mitochondrial membrane protein mitoNEET, published in Nature Medicine in 2012 and earlier in the Journal of Biological Chemistry in 2007, suggested that altering mitochondrial activity can influence insulin sensitivity and oxidative capacity. Taken together, the new work on MENTSH strengthens the case for treatments aimed at the mitochondria themselves, with the possibility of more precise approaches for obesity, insulin resistance and related metabolic disorders.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
