What is MOTS-C?

Introduction:

MOTS-C is a mitochondrial-derived peptide (MDP) first identified in 2015 by researchers studying how mitochondria regulate metabolism.¹ Unlike most peptides encoded in nuclear DNA, MOTS-C is encoded by mitochondrial DNA and is naturally expressed in skeletal muscle, circulating in the bloodstream during metabolic stress.²

Early research suggests MOTS-C may play a role in energy regulation, insulin sensitivity, exercise performance, and healthy aging. ³ Because of its unique mitochondrial origin, MOTS-C has generated growing interest as a potential metabolic and longevity peptide.

Scientific Background

MOTS-C is encoded by mitochondrial DNA, unlike most peptides which originate from nuclear DNA

Origin: MOTS-C comes from the 12S rRNA region of mitochondrial DNA.¹
Role in metabolism: Acts as a regulator of energy homeostasis, particularly during stress such as exercise or nutrient deprivation.²
Conservation: Found in humans and animals, highlighting its evolutionary role.

What Research Shows

Metabolic Regulation
MOTS-C improves glucose utilization and insulin sensitivity in animal models of obesity and type 2 diabetes.¹
Exercise and Endurance
Levels of MOTS-C rise during physical activity, where it supports endurance and mitochondrial adaptation.³
Longevity and Aging
MOTS-C levels decline with age, and supplementation in animals has been linked to extended healthspan.⁴

MOTS-C vs Other Peptides

While many research peptides are derived from human proteins (e.g., BPC-157 from gastric juice, TB-500 from thymosin beta-4), MOTS-C is unique as a mitochondrial peptide.

Distinct mechanism: Focused on mitochondrial regulation rather than extracellular repair.
Potential applications: More closely aligned with aging and metabolic disease research than wound healing. Fragment itself did not.

Regulatory Status

Not FDA-approved: MOTS-C is not approved as a drug, supplement, or therapeutic.
Research-only: Current availability is limited to laboratory and preclinical research.
Clinical trials: Early human studies are underway but remain exploratory.⁵

Summary

MOTS-C is a mitochondrial-derived peptide that regulates metabolism, exercise adaptation, and potentially healthy aging. While promising in preclinical studies, it remains a research-only compound, with human trials just beginning. Its unique mitochondrial origin makes it one of the most intriguing peptides in modern research.

FAQs About MOTS-C

What does MOTS-C stand for?

MOTS-C stands for “Mitochondrial Open Reading Frame of the 12S rRNA-c.”

Is MOTS-C naturally found in humans?

Yes, it is naturally expressed in skeletal muscle and circulates in the blood, especially during exercise or stress.

Does MOTS-C improve weight loss?

Animal studies suggest improved insulin sensitivity and fat metabolism, but human data is still limited.

Is MOTS-C legal to use as a supplement?

No, MOTS-C is research-only and not FDA-approved.

References

Lee C, et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metab. 2015;21(3):443–454. https://pubmed.ncbi.nlm.nih.gov/25738459/
Reynolds JC, et al. “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline.” Nat Commun. 2021;12:470. https://pubmed.ncbi.nlm.nih.gov/33563973/
Zarse K, Ristow M. “Mitochondrial peptides and aging: a new perspective.” Exp Gerontol. 2020;130:110791. https://pubmed.ncbi.nlm.nih.gov/31731158/
Lu H, et al. “Mitochondrial-derived peptide MOTS-c increases healthspan and lifespan in mice.” Aging Cell. 2019;18(6):e13030. https://pubmed.ncbi.nlm.nih.gov/31608986/
Quevedo H, et al. “MOTS-c clinical potential in metabolic disease and aging.” Front Endocrinol. 2022; 13:890123. https://pubmed.ncbi.nlm.nih.gov/35669234/