Emerging Research

MOTS-c

Longevity & Anti-Aging · ['Mitochondrial ORF of the 12S rRNA type-c', 'Mitochondrial-derived peptide MOTS-c']

MOTS-c is a 16-amino-acid mitochondrial-derived peptide studied for effects on metabolic homeostasis, insulin sensitivity, and exercise capacity through AMPK-related signaling in preclinical models.

🔬 Research use only — not for human or veterinary use. K4 Elite does not provide dosing instructions.

Molecular Formula

C101H152N28O22S2

Molecular Weight

2174.6 g/mol

PubChem

CID 146675088 ↗

Research Level

Emerging Research

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MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome. It belongs to the class of mitochondrial-derived peptides and was first described by researchers at the University of Southern California.

Preclinical research has focused on its role in metabolic regulation, particularly insulin sensitivity, glucose homeostasis, and metabolic adaptation to exercise and aging. It is notable as an example of a bioactive peptide originating from mitochondrial DNA that appears to act as a signaling molecule.

MOTS-c is presented as a research reference peptide. It is investigational and has not been approved for clinical use.

MOTS-c has been reported to activate the AMP-activated protein kinase (AMPK) pathway and to influence folate-methionine cycle and de novo purine biosynthesis, linking it to cellular energy sensing and metabolic flexibility.

Studies also describe MOTS-c translocating to the nucleus under metabolic stress, where it is proposed to regulate stress-response gene expression (including antioxidant-response pathways), providing a mechanism by which a mitochondrial peptide can modulate nuclear gene programs.

Regulation of insulin sensitivity and glucose homeostasis in rodent models (Lee et al., 2015).
AMPK activation and metabolic flexibility under nutrient and exercise stress.
Nuclear translocation and stress-response gene regulation (Kim et al., 2018).
Effects on physical capacity and exercise performance in aged mice (Reynolds et al., 2021).
Age-associated decline of circulating MOTS-c as a metabolic biomarker.

📋 How published studies were conducted — a research reference summarizing study designs from the literature. This is not usage, dosing, or administration guidance. K4 Elite does not provide dosing instructions; determining any research protocol is the sole responsibility of the qualified researcher.

Lee and colleagues (2015) administered MOTS-c to mice and reported enhanced insulin sensitivity and resistance to diet-induced obesity, using glucose tolerance and insulin tolerance tests as outcome measures; the study linked these effects to AMPK activation and the folate-methionine cycle [1].

Kim and colleagues (2018) demonstrated in cell and mouse models that MOTS-c translocates to the nucleus under metabolic stress, using gene-expression profiling to show regulation of antioxidant and stress-response genes [2].

Reynolds and colleagues (2021) studied MOTS-c in young and aged mice, measuring running capacity and physical performance, and reported improvements in exercise capacity in treated aged animals at the doses used in that study [3].

Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.

AMPK pathwaySynergistic

MOTS-c activates AMPK signaling, central to its proposed metabolic effects in research models.

Insulin / insulin signalingSynergistic

Studies report enhanced insulin sensitivity, indicating interaction with glucose-handling pathways.

Exercise / physical trainingCompatible

MOTS-c responses overlap with exercise-induced metabolic adaptation in animal studies.

MetforminNeutral

Both engage AMPK signaling; combined effects are not established in the literature.

Folate-methionine cycle metabolitesNeutral

MOTS-c influences this metabolic cycle; a relevant variable in experimental design.

What is MOTS-c?

MOTS-c is a 16-amino-acid mitochondrial-derived peptide studied for roles in metabolic regulation, insulin sensitivity, and exercise adaptation.

How does MOTS-c work in research models?

Studies describe activation of the AMPK pathway, effects on the folate-methionine cycle, and nuclear translocation to regulate stress-response genes.

Why is MOTS-c interesting for aging research?

Circulating MOTS-c declines with age, and preclinical work links it to metabolic flexibility and physical capacity, making it a focus of aging and metabolism studies.

Is MOTS-c an approved therapy?

No. MOTS-c is investigational, with evidence primarily from cell and rodent studies; it is not approved for clinical use.

Can this product be consumed?

No. This peptide is supplied for laboratory research use only and is not intended for human or veterinary use, diagnosis, or treatment.

Disclaimer: This profile summarizes published preclinical and laboratory research for reference only. It is not medical advice and makes no claim of safety or efficacy in humans. Determining any research protocol is the sole responsibility of the qualified researcher. Products are sold strictly for in-vitro research and have not been evaluated by the FDA.