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Peer-Reviewed Research

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a mitochondrial-derived peptide involved in cellular energy metabolism, stress adaptation, insulin sensitivity, mitochondrial function, and metabolic homeostasis. Recent research has investigated its potential role in obesity, diabetes, cardiovascular disease, aging, exercise physiology, and mitochondrial biology. While human research is expanding, much of the mechanistic evidence remains preclinical.

Original Research

Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart

Journal: Frontiers in Physiology
Published: 2025
Study Type: Original laboratory and preclinical research

Summary

Researchers evaluated MOTS-c in experimental models of type 2 diabetic cardiomyopathy. Treatment improved mitochondrial respiration, enhanced ATP production, and restored multiple markers of mitochondrial function. The findings support continued investigation of MOTS-c in metabolic and cardiovascular research.

Read Full Text:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12257629/

MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis

Journal: Acta Biochimica et Biophysica Sinica
Published: 2024
Study Type: Original preclinical research

Summary

This study investigated MOTS-c in a mouse model of cancer-induced bone pain. Researchers reported reduced pain behaviors, improved mitochondrial biogenesis, decreased inflammatory signaling, and reduced bone destruction through AMPK-mediated mechanisms. These findings remain preclinical and require validation in human studies.

View on PubMed:
https://pubmed.ncbi.nlm.nih.gov/38716540/

Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss

Journal: Journal of Clinical and Translational Endocrinology
Published: 2025
Study Type: Human observational study

Summary

Researchers compared circulating MOTS-c concentrations between lean adults and adults with obesity. Higher circulating MOTS-c levels were associated with obesity and insulin resistance, while concentrations remained largely unchanged following bariatric surgery despite substantial weight loss. The authors suggested MOTS-c may represent a compensatory metabolic response requiring further investigation.

View on PubMed:
https://pubmed.ncbi.nlm.nih.gov/41551324/

Reduced serum levels of mitochondria-derived peptide MOTS-c in patients with obstructive sleep apnea

Journal: Sleep and Biological Rhythms
Published: 2025
Study Type: Human observational study

Summary

This clinical study examined serum MOTS-c concentrations in adults with obstructive sleep apnea. Lower circulating MOTS-c levels were associated with increasing disease severity, body mass index, and oxygen desaturation indices, supporting further investigation of MOTS-c as a metabolic biomarker in sleep disorders.

View on PubMed:
https://pubmed.ncbi.nlm.nih.gov/40538389/

Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes

Journal: Experimental & Molecular Medicine
Published: 2025
Study Type: Original laboratory and preclinical research

Summary

Researchers investigated MOTS-c in pancreatic islet aging and diabetes models. Treatment reduced cellular senescence, improved glucose regulation, and altered gene-expression pathways associated with β-cell aging. The findings support continued investigation of MOTS-c in metabolic disease research.

View on PubMed:
https://pubmed.ncbi.nlm.nih.gov/40855115/

Review Articles

Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging

Journal: Journal of Translational Medicine
Published: 2023
Study Type: Scientific review

Summary

This review summarizes current knowledge regarding MOTS-c biology, including its effects on cellular stress responses, mitochondrial function, insulin sensitivity, inflammation, exercise physiology, metabolism, and healthy aging. It also discusses proposed molecular pathways and future research directions.

View on PubMed:
https://pubmed.ncbi.nlm.nih.gov/36670507/

Read Full Text:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9854231/

The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis

Journal: Diabetology & Metabolic Syndrome
Published: 2024
Study Type: Systematic review and meta-analysis

Summary

This systematic review evaluated circulating mitochondrial-derived peptides, including MOTS-c, across metabolic disorders. The authors analyzed relationships between MOTS-c concentrations, obesity, insulin resistance, diabetes, and metabolic syndrome while highlighting variability among published studies and the need for additional standardized clinical research.

Read Full Text:
https://link.springer.com/article/10.1186/s13098-024-01405-w

Additional MOTS-c Publications

Browse current PubMed research:
https://pubmed.ncbi.nlm.nih.gov/?term=MOTS-c

Research Disclaimer

The information presented in this Research Library is provided for educational and scientific reference purposes only and is based on published peer-reviewed research. Research findings continue to evolve, and investigational compounds may not be approved for clinical use. All Pearland Peptides products are supplied For Research Use Only and are not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease.

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