MOTS-c Lyophilized Powder

Overview

MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA Type-c; CAS 1627580-86-2) is a 16-amino acid peptide with the sequence MRWQEMGYIFYPRKLR, encoded within the 12S ribosomal RNA gene of human mitochondrial DNA — an unexpected location for a bioactive peptide, given that the mitochondrial genome was previously thought to encode only components of the oxidative phosphorylation machinery. Identified by Lee et al. in 2015, MOTS-c represents a founding member of a growing class of mitochondria-derived peptides (MDPs) that function as retrograde signals from the mitochondria to the nucleus and other cellular compartments, coordinating systemic metabolism in response to mitochondrial stress.

MOTS-c’s primary characterized mechanism involves translocation to the nucleus under metabolic stress conditions, where it regulates gene expression programs that control glucose uptake, fatty acid oxidation, and adaptive thermogenesis. Its effects on the AMPK pathway — a central energy-sensing kinase that coordinates glucose and lipid metabolism — position MOTS-c as a research tool for metabolic disease, insulin resistance, and exercise biology. Circulating MOTS-c levels decline with age in humans and are reduced in patients with type 2 diabetes and obesity, consistent with its proposed role as a metabolic stress-responsive signal that declines as part of the aging process.

Technical Specifications

Key Research Findings

The landmark discovery paper by Lee et al. published in Cell Metabolism in 2015 identified MOTS-c as a mitochondria-encoded peptide that promotes metabolic homeostasis and reduces insulin resistance [1]. In diet-induced obese mouse models, systemic MOTS-c administration significantly reduced body weight, improved insulin sensitivity, and enhanced glucose tolerance — effects mediated through AMPK activation and downstream regulation of the GLUT4 glucose transporter. Notably, MOTS-c recapitulated aspects of the metabolic response to exercise in sedentary animals, positioning it as a potential exercise-mimetic peptide and generating substantial interest for obesity and metabolic syndrome research.

Subsequent work by Kim et al. in Nature Communications in 2021 expanded the mechanistic understanding of MOTS-c, demonstrating that it functions as a mitochondrial stress-responsive signal that translocates to the nucleus under stress conditions to regulate nuclear gene expression — establishing MOTS-c as a bona fide mitochondria-to-nucleus retrograde signal rather than simply a circulating hormone-like factor [2]. This nuclear function, operating through direct interaction with transcription factors including ATF1, broadens MOTS-c’s relevance to researchers studying mitochondrial-nuclear crosstalk, cellular stress response, and the biology of aging beyond its metabolic effects.

Why Purity Matters

MOTS-c’s 16-amino acid sequence includes residues susceptible to oxidation (methionine at positions 1 and 6) and sequence-specific folding that influences its cellular uptake and nuclear localization behavior. Oxidized methionine variants can exhibit reduced biological activity in AMPK activation assays and altered cellular trafficking compared to the correctly reduced form. Given MOTS-c’s relatively recent characterization and the sensitivity of its downstream readouts (AMPK phosphorylation, nuclear translocation, gene expression changes), batch-level HPLC purity at ≥99% with MS identity confirmation is essential for reproducible experimental outcomes. For researchers building MOTS-c protocols, supplier documentation that includes MS verification of the correct 16-AA sequence is the minimum standard for a qualified raw material.

References:
[1] Lee C, et al. The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Cell Metab. 2015;21(3):443–54. PMID: 25738458
[2] Kim SJ, et al. MOTS-c Is an Exercise-Induced Mitochondrial-Encoded Regulator of Age-Dependent Physical Decline and Muscle Homeostasis. Nat Commun. 2022;13(1):1873. PMID: 35388002

Quality & Documentation

Each batch of MOTS-c lyophilized powder is individually tested before shipment. Included with every order:

• HPLC purity verification (≥99%)
• Mass spectrometry (MS) identity confirmation
• Batch number for full traceability

COA available upon request before order commitment.

Ordering Information

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FAQ

Q: What is the difference between MOTS-c and humanin?
Both MOTS-c and humanin are mitochondria-derived peptides (MDPs) encoded within the mitochondrial genome, but they differ in sequence, size, and primary biological effects. Humanin (CAS 330936-69-1) is a 21-AA peptide encoded in the 16S rRNA region, primarily studied for neuroprotective and anti-apoptotic effects. MOTS-c is a 16-AA peptide encoded in the 12S rRNA region, primarily characterized for metabolic regulation through AMPK and nuclear gene expression programs. Both are available from Vitaconin with individual COA documentation.

Q: Is MOTS-c related to exercise physiology?
Yes. Circulating MOTS-c levels increase in response to physical exercise in humans, and MOTS-c administration in animal models recapitulates aspects of the metabolic adaptation to exercise — including improved insulin sensitivity, enhanced fatty acid oxidation, and resistance to diet-induced obesity. This exercise-mimetic profile is one of the primary reasons MOTS-c is studied in the contexts of metabolic disease, aging, and physical performance research.

Q: How should MOTS-c be stored?
Store unreconstituted lyophilized MOTS-c at −20°C, sealed, away from light and moisture. Shelf life is 24 months under proper conditions. Once reconstituted, store at 2–8°C and use within the timeframe specified in the COA.