MOTS-c Peptide

MOTS-c (mitochondrial open-reading-frame of the 12S rRNA-c) is a recently discovered peptide derived from mitochondria. Composed of 16 amino acids, it is expressed in tissues and plasma, suggesting both cell-specific and hormonal functions. MOTS-c is thought to act through activation of the AMP-activated protein kinase (AMPK) pathway. Alongside Humanin, MOTS-c is one of the few mitochondrial-derived peptides (MDPs) studied for its role in metabolic regulation. Under metabolic stress, MOTS-c may move to the nucleus to influence gene expression and can also be secreted extracellularly, earning the nickname “mitochondrial hormone” or “mitokine.”

Chemical Makeup

• Molecular Formula: C101H152N28O22S2
• Molecular Weight: 2174.64 g/mol
• Other Names: Mitochondrial-derived peptide MOTS-c, Mitochondrial open reading frame of the 12S rRNA-c

Research and Clinical Studies

Animal studies have revealed that MOTS-c may enhance physical performance, regulate cellular metabolism, and support myoblast adaptation. Research indicates that MOTS-c expression may decline with age, potentially contributing to age-related metabolic dysfunction. MOTS-c also appears to interact with longevity regulators like NAD+ and sirtuins, suggesting a role in cellular aging and lifespan modulation. Endogenous MOTS-c levels may be increased through physical activity, potentially enhancing overall cellular metabolism.

MOTS-c Peptide and Muscle Metabolism

As people age, skeletal muscles often develop insulin resistance, reducing glucose uptake. MOTS-c exposure may enhance AMPK activation in muscle cells, improving glucose transporter expression and skeletal muscle metabolism. The peptide also appears to target metabolic pathways such as the folate-methionine cycle and purine biosynthesis, potentially shifting cellular energy balance and influencing glucose and lipid utilization. As a mitochondrial hormone, MOTS-c may regulate systemic metabolism, affecting skeletal muscle and possibly adipose tissue, and contribute to glucose homeostasis and insulin sensitivity across multiple tissues.