MOTS-c (revision 22)

MOTS-c is a 16-residue peptide encoded within the mitochondrial genome rather than the nuclear genome, and is one of a small group of mitochondria-derived peptides identified since the 2000s. It is not approved for any indication.^[1]

Its proposed physiological role is as a signal from mitochondria to the rest of the cell and to distant tissues, influencing metabolic homeostasis. In rodent work it has been reported to improve insulin sensitivity and to protect against diet-induced obesity, through effects converging on AMP-activated protein kinase.^[1]

Human evidence is very limited. Circulating concentrations have been measured and associated with metabolic phenotypes in observational studies, and controlled interventional data are sparse.^[2]

The mitochondrial genome was long thought to encode only 13 proteins, all components of the respiratory chain. Short open reading frames within mitochondrial ribosomal RNA genes were subsequently found to encode small peptides, of which humanin was the first and MOTS-c one of the better characterised.^[1]

The genomic origin has a practical consequence: mitochondrial DNA is maternally inherited and accumulates variants differently from nuclear DNA, so polymorphism in these peptides follows mitochondrial haplogroup rather than ordinary Mendelian patterns.^[2]

Detection and quantification are analytically demanding. Short peptides at low circulating concentration require sensitive and specific methods, and reported concentrations differ between studies using different assays — the same caution that applies to any peptide immunoassay. See Proglucagon for a worked example of the problem.^[2]

In rodents, administration has been reported to improve insulin sensitivity, increase glucose disposal, and attenuate diet-induced obesity, with AMP-activated protein kinase activation the proposed common mechanism.^[1]

In humans, exercise increases circulating MOTS-c, and lower concentrations have been associated with obesity and insulin resistance in cross-sectional studies. Association of that kind cannot establish direction: lower concentrations may contribute to the phenotype or result from it.^[2]

No adequately powered controlled trial of administration in humans has reported. The gap between the preclinical literature and the human evidence is wide, and it should not be closed by inference.^[1]

MOTS-c is offered by research-chemical suppliers. It is unapproved, and this wiki does not represent it as suitable for human use; see Research use only.^[3]

As a 16-residue peptide it is a straightforward synthesis relative to the incretin analogues, and the documentary considerations are the ordinary ones: identity by mass, purity by a named chromatographic method, and content with water and counterion if the mass of peptide in a vial is to be known.^[4]

The absence of a marketed product means no generally available reference standard, so identity rests on mass agreement with a calculated value rather than comparison with an authenticated material.^[4]

• Research use only
• Peptide content
• Certificate of analysis