Metabolic & Incretin Research Guide

MOTS-C: Mechanism, Handling & Research Guide

Also known as: Mitochondrial ORF of the 12S rRNA type-c, MOTSc

Key Facts

MOTS-C is a metabolic & incretin research peptide (C101H152N28O22S2, MW 2174.64 g/mol). Mitochondrial-derived peptide for metabolic regulation and cellular energy research. It is supplied as a lyophilized powder for laboratory and in-vitro research use only — not for human consumption.

Classification	Mitochondrial-derived peptide
Molecular Formula	C101H152N28O22S2
Molecular Weight	2174.64 g/mol
CAS Number	1627580-64-6
Research Half-Life	Short circulating half-life in preclinical models
Form	Lyophilized powder
Research Category	Metabolic & Incretin

What is MOTS-C?

MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA type-c) is a 16-amino acid peptide encoded within the mitochondrial genome, specifically within the 12S rRNA gene. Its primary mechanism of action involves activation of the AMPK pathway, which regulates cellular energy homeostasis by promoting glucose uptake and fatty acid oxidation independent of insulin signaling. Research published by Lee et al. (Cell Metabolism, 2015) demonstrated that MOTS-c use in diet-induced obese mice significantly improved glucose tolerance and reduced fat accumulation without altering food intake. Subsequent studies from the same USC laboratory showed that MOTS-c levels decline with age in human plasma, and that exercise increases circulating MOTS-c levels, suggesting it functions as a mitochondrial-derived exercise mimetic. Unlike traditional metabolic peptides that target specific membrane receptors, MOTS-c is unique in that it translocates to the nucleus under metabolic stress to regulate nuclear gene expression, particularly genes involved in the methionine-folate cycle and de novo purine biosynthesis. Compared to other mitochondrial-derived peptides like humanin, MOTS-c appears more specifically involved in metabolic regulation rather than cytoprotection. The lyophilized peptide should be stored at -20C and protected from light; reconstitute with bacteriostatic water and store reconstituted solutions at 2-8C for up to 21 days. MOTS-c is primarily researched by aging biology laboratories, exercise physiology departments, and mitochondrial medicine research centers investigating metabolic signaling peptides.

MOTS-C Research Applications

In published and preclinical research, MOTS-C has been studied across the following areas:

Glucose regulation and insulin sensitivity
Skeletal muscle energy and endurance
Fat oxidation and adipose tissue studies
Cellular-aging and senescence research

MOTS-C in Research: Study Context

MOTS-c is a 16-amino-acid mitochondrial-derived peptide studied for its role in metabolic homeostasis, insulin sensitivity and exercise-mimetic signaling via AMPK. Research concentrations are model-specific. The lyophilized peptide is reconstituted with bacteriostatic water for laboratory use only.

How MOTS-C Compares

Researchers frequently evaluate MOTS-C alongside related compounds:

MOTS-C vs 5-Amino-1MQ — MOTS-c is a mitochondrial-derived peptide studied around AMPK/insulin sensitivity; 5-Amino-1MQ is an NNMT inhibitor affecting NAD+/methylation-linked adipocyte metabolism.

MOTS-C — Frequently Asked Questions

Is MOTS-C legal to buy for research?

MOTS-C is sold in the United States as a research chemical for laboratory and in-vitro use only. It is not approved by the FDA for human use and is not sold for human consumption. Researchers are responsible for compliance with all applicable federal, state, and institutional regulations.

Does MOTS-C come with a Certificate of Analysis?

Yes. Every batch of MOTS-C from Elyte Peptides ships with a third-party Certificate of Analysis (COA) documenting identity and HPLC purity (≥98%), so research results can be traced to a verified lot.

What is MOTS-C and how does it work?

MOTS-C is a mitochondrial-derived peptide (MDP) encoded by the 12S rRNA gene within mitochondrial DNA. It is a 16-amino acid peptide that has been observed to activate AMPK (AMP-activated protein kinase) signaling, which plays a central role in cellular energy homeostasis. In preclinical models, MOTS-C translocates to the nucleus under metabolic stress and regulates gene expression related to glucose metabolism and fatty acid oxidation.

What research has been done on MOTS-C?

Research published by Dr. Changhan David Lee's lab at USC (Cell Metabolism, 2015) first identified MOTS-C as a mitochondrial-encoded signaling peptide. Subsequent studies demonstrated that MOTS-C use improved glucose regulation in diet-induced obesity mouse models. Additional published research has examined its role in skeletal muscle metabolism during exercise, age-related metabolic decline, and insulin sensitivity in high-fat diet models.

How does MOTS-C compare to Humanin?

Both MOTS-C and Humanin are mitochondrial-derived peptides (MDPs), but they have distinct mechanisms. Humanin primarily acts through cytoprotective and anti-apoptotic pathways via STAT3 signaling, while MOTS-C activates AMPK to regulate metabolic homeostasis. MOTS-C is a shorter peptide (16 amino acids vs. 24 for Humanin) and has been more extensively studied for its effects on glucose metabolism and exercise physiology.

Research References

Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metab 2015.

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