MOTS-c
Mitochondrial-derived peptide
A mitochondrial-derived peptide studied in metabolic regulation and exercise research.
Also referenced as: Mitochondrial ORF of the 12S rRNA type-c, MOTSc
Overview
MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the MT-RNR1 (12S rRNA) region of mitochondrial DNA. It was described in 2015 and is one of a small family of mitochondrial-derived peptides.
At a glance
What MOTS-c does
MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region, making it one of a small class of peptides written in the mitochondrial rather than nuclear genome. Its defining action in research is metabolic regulation through AMPK activation. Mechanistically, MOTS-c inhibits the folate cycle and its downstream de novo purine biosynthesis, causing accumulation of AICAR (an endogenous AMP mimetic), which in turn activates AMPK, the cell's master energy-sensing kinase. Skeletal muscle appears to be its primary target tissue. Under metabolic stress, MOTS-c also translocates to the nucleus and acts on stress-response gene expression, giving it a role as a signal that coordinates the cell's response to energy demand.
Downstream, AMPK activation by MOTS-c enhances insulin-independent glucose uptake, increases fatty-acid beta-oxidation, and improves whole-body insulin sensitivity. In mouse studies, MOTS-c administration prevented both age-dependent and high-fat-diet-induced insulin resistance and protected against diet-induced obesity, with roughly a 30% increase in the glucose infusion rate needed to maintain euglycemia during insulin clamps, a direct readout of improved insulin sensitivity. Because it reproduces several exercise-like metabolic adaptations, it is often described as an exercise-mimetic peptide. Human data are so far correlational rather than interventional: circulating MOTS-c levels have been found reduced in certain obese populations, and levels rise with exercise, but there are no completed controlled human efficacy trials, so the functional claims rest on animal and cell evidence.
Effects reported in research
- Activates AMPK, the master cellular energy sensor, by inhibiting the folate cycle and raising endogenous AICAR (mechanistic/animal).
- Enhances insulin-independent glucose uptake in skeletal muscle (its primary target tissue).
- Improved whole-body insulin sensitivity (~30% higher glucose infusion rate in mouse insulin clamps).
- Increased fatty-acid beta-oxidation, limiting fat accumulation in diet-induced obese mice.
- Prevented age-dependent and high-fat-diet-induced insulin resistance in mouse models.
- Protected against diet-induced obesity in rodents.
- Translocates to the nucleus under metabolic stress to regulate stress-adaptive gene expression (cell-based data).
- In humans, circulating levels are reduced in some obese populations and rise with exercise — associative only, no completed interventional efficacy trials.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
MOTS-c is reported to regulate metabolic homeostasis, in part via activation of the AMPK pathway and modulation of the folate-methionine cycle and de novo purine biosynthesis. It has been described to translocate to the nucleus under metabolic stress and influence stress-response gene expression. Preclinical work links it to improved insulin sensitivity and glucose uptake in skeletal muscle; it is also described as exercise-responsive.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which MOTS-c appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- A genuine peptide encoded by mitochondrial DNA (mitochondrial-derived peptide)
- 16 amino acids; sequence MRWQEMGYIFYPRKLR
- Associated with AMPK activation and metabolic-stress adaptation in preclinical studies
- Levels reported to change with exercise and age
- Evidence is predominantly preclinical; not an approved therapeutic
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. MOTS-c is a research compound.
Reported research dosing comes from rodent studies rather than established human protocols. Published mouse work used systemic dosing on daily or intermittent schedules. These are figures reported for research context only, not dosing guidance for humans.
- Rodent studies: reported at ~15 mg/kg/day for ~2 weeks
- Rodent studies (intermittent): reported at ~15 mg/kg dosed ~3x/week
Human pharmacokinetics and dosing are not established; no completed published human trials. Reference figures only.
How it compares
Unlike the GH-derived fragments here, MOTS-c is endogenously encoded in the mitochondrial genome and acts as a broad metabolic regulator rather than a targeted lipolytic fragment.
Commonly studied alongside
Compounds frequently researched together with MOTS-c in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Compare and calculate
Side-by-side pages for the pairings the literature already documents for MOTS-c, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
MOTS-c reconstitution calculator → Concentration, volume per measured amount and syringe units for a stated vial mass and diluent volume. A unit-conversion reference, not a dosing recommendation.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
MOTS-c sits in the Metabolic & Mitochondrial area of the PeptiDex library.
- Entry type: Research compound reference
- Metabolic & Mitochondrial category hub →
- Browse the full library →
- Glossary of terms →
Where researchers source MOTS-c
For researchers studying MOTS-c, third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.
View research-supplier listing →
Outbound link to a third-party research supplier. Inclusion does not constitute endorsement; all editorial content is developed independently.
Frequently asked questions
What is MOTS-c and where does it come from?
MOTS-c (Mitochondrial Open-reading-frame of the Twelve-S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the 12S rRNA region of mitochondrial DNA, rather than by the nuclear genome. First described in 2015, it is studied as a regulator of metabolic homeostasis. Its sequence and MDP origin make it structurally distinct from most catalog peptides.
What is MOTS-c studied for?
MOTS-c is studied in models of metabolic homeostasis, insulin sensitivity, exercise capacity, and aging. Research reported that MOTS-c levels rise with exercise and that exogenous MOTS-c improved glucose tolerance, insulin sensitivity, and running endurance in aged mice. It is thought to act partly via AMPK-linked metabolic signaling.
How is MOTS-c thought to work mechanistically?
MOTS-c is reported to translocate to the nucleus under metabolic stress and influence adaptive gene-expression programs, and it engages the AMPK pathway and folate/one-carbon metabolism to promote glucose uptake and fatty-acid oxidation. This positions it as a signaling peptide linking mitochondrial state to whole-body metabolism in preclinical models.
What does MOTS-c's pharmacokinetic profile imply for research design?
The pharmacokinetics of exogenous MOTS-c (bioavailability, distribution, half-life, clearance) are incompletely characterized in the literature, and no completed human clinical trials have been published. Rodent studies have used both daily and intermittent (e.g., 3x/week) dosing schedules, which reflects this uncertainty. Researchers should treat protocol parameters as provisional.
How should MOTS-c be reconstituted and stored?
MOTS-c is supplied as a white to off-white lyophilized powder, soluble in water, and is typically reconstituted with bacteriostatic or sterile water. Lyophilized peptide is stored refrigerated (2-8 C) or frozen for longer terms, with reconstituted solution kept refrigerated. A COA with HPLC purity and mass identity is standard.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.
References
Primary literature indexed in PubMed for MOTS-c. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress
- Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging
Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.