Breakthrough in Mitochondrial-Derived Peptide MOTS-c Research Offers New Treatment Potential for Multiple Diseases

Recent studies on the mitochondrial-derived peptide MOTS-c have revealed that this short peptide encoded by mitochondrial DNA not only plays a role in the diagnosis and treatment of chronic hepatitis B but also inhibits the progression of ovarian cancer. It may also serve as a potential therapeutic target for non-alcoholic fatty liver disease and diabetic cardiomyopathy.

Recently, the internationally renowned journal GUT (CAS Q1 TOP, IF: 24.5) published online the research findings of Professor Oi Shui Sui’s team from the First Affiliated Hospital of Fujian Medical University. The study identified a mitochondrial-derived short peptide, MOTS-c, which functions as a regulator of mitochondrial dynamics in the diagnosis and treatment of chronic hepatitis B.

Simultaneously, several other independent studies have indicated that MOTS-c shows potential therapeutic value for a variety of diseases, including ovarian cancer, non-alcoholic fatty liver disease, and diabetic cardiomyopathy.

01 New Strategy for Treating Chronic Hepatitis B

Research by Professor Oi Shui Sui’s team found that after HBV infection, endogenous MOTS-c levels decrease in the human body, and MOTS-c expression is significantly negatively correlated with serum HBV DNA levels.

In cell and animal models, MOTS-c exhibited antiviral effects and improved liver function. The mechanism of action is closely related to two factors: first, it inhibits HBV replication by activating mitochondrial antiviral signaling proteins and downstream signaling pathways; second, it maintains mitochondrial homeostasis through MYH9-actin molecular motor-mediated mitochondrial remodeling.

This discovery provides new insights for the diagnosis and treatment of HBV infection and other mitochondrial-related diseases.

02 New Discovery in Inhibiting Ovarian Cancer Progression

Research by Li Jibin / Yang Hong’s team from the Air Force Medical University, published in Advanced Science, showed that MOTS-c expression is downregulated in ovarian cancer, and low MOTS-c expression is associated with a poor prognosis.

Exogenous MOTS-c inhibited the growth of ovarian cancer cells in vitro and in vivo. Mechanistically, MOTS-c exerts its anti-cancer effects by attenuating USP7-mediated LARS1 deubiquitination and promoting LARS1 degradation.

Studies showed that MOTS-c treatment significantly suppressed the growth of OC cells, reducing tumor volume and weight. Immunohistochemical analysis revealed that LARS1 expression was significantly reduced after MOTS-c treatment, and no obvious signs of toxicity were found.

03 Potential Treatment for Non-Alcoholic Fatty Liver Disease

A research team from the Fourth Military Medical University reported in Cell Reports that MOTS-c interacts with the BH3 domain of Bcl-2.

Mechanistic studies indicated that MOTS-c increases Bcl-2 protein stability and inhibits its ubiquitination, thereby suppressing the development of NASH. MOTS-c treatment significantly reversed hepatocyte steatosis, inhibited large lipid droplet deposition, and alleviated the progression of hepatocyte apoptosis, inflammation, and fibrosis.

Metabolomic analysis showed that MOTS-c treatment partially reversed the metabolic disorders caused by NASH and maintained mitochondrial homeostasis.

04 New Direction for Treating Diabetic Cardiomyopathy

Research indicates that MOTS-c also has therapeutic potential for diabetic cardiomyopathy. Researchers conducted studies using a streptozotocin (STZ)-induced type I diabetic mouse model.

Results showed that MOTS-c improved cardiac function, reduced myocardial hypertrophy, fibrosis, and cell apoptosis. At the molecular level, MOTS-c activated adenosine monophosphate-activated protein kinase (AMPK) in the hearts of diabetic mice and reduced myocardial inflammation.

This provides a new direction for the treatment of diabetic cardiomyopathy. Although there are some limitations, MOTS-c is expected to become an effective drug for treating diabetic cardiomyopathy.

05 Multifunctional Bioactivity of MOTS-c

MOTS-c is a secretory short peptide encoded by mitochondrial 12S rRNA, consisting of 16 amino acids. It possesses multiple biological activities, including mitochondrial signal transduction.

Under conditions of metabolic stress, MOTS-c translocates to the nucleus and binds to transcription factors, regulating nuclear gene expression and maintaining cellular homeostasis. In recent years, MOTS-c has been identified as a key factor involved in the regulation of mitochondrial retrograde signaling.

06 Clinical Significance and Future Prospects

Multiple research results suggest that MOTS-c could become a potential diagnostic marker and therapeutic target for various diseases.

For ovarian cancer patients, MOTS-c may no longer be an out-of-reach drug but an anticipated therapeutic target. Although research is still ongoing, this discovery undoubtedly opens new directions for future treatment plans.

Similarly, MOTS-c may bring new treatment hope for patients with chronic hepatitis B, non-alcoholic fatty liver disease, and diabetic cardiomyopathy.

With more clinical trials underway, MOTS-c is expected to move from basic research to clinical practice, providing new treatment options for patients with various diseases.

Future research will continue to explore the mechanisms and clinical applications of MOTS-c, promoting its transition from the laboratory to the clinic and bringing hope to more patients.