All information below describes the compound's chemical identity, laboratory handling, and the published research literature. It describes molecular targets and results in laboratory and animal models only — not effects in humans — and is not evidence of any human benefit.
What Is MOTS-C?
MOTS-C (Mitochondrial Open-reading-frame of the Twelve S rRNA type-C) is a mitochondrial-derived peptide — a class of small signaling microproteins encoded within the mitochondrial genome rather than the nuclear genome. It was originally characterized by Lee and colleagues in 2015 as a peptide translated from a short open reading frame in the 12S rRNA region of mitochondrial DNA. It is catalogued in the literature with molecular formula C100H152N28O22S2 and CAS 1901518-07-7.
It is supplied as a reference compound for in vitro and animal research use only. The sections below summarize its chemical identity, laboratory handling, the molecular targets and model systems examined in the published literature, and the primary references — without describing outcomes, efficacy, or effects in humans.
Research Targets & Pathways
Published preclinical and observational literature has examined MOTS-C in relation to several molecular systems. These are pathway associations reported in laboratory, animal, and observational cohort studies; refer to the cited studies for methods and findings.
- AMPK signaling — examined in relation to AMP-activated protein kinase phosphorylation and downstream metabolic gene regulation.
- Nuclear translocation / gene regulation — examined in relation to MOTS-C nuclear localization and AMPK-dependent transcriptional regulation under metabolic stress.
- Glucose transport & insulin signaling — examined in relation to glucose transporter expression and insulin signaling pathways in skeletal muscle cell systems.
- Fatty acid oxidation / mitochondrial respiration — examined in relation to substrate oxidation rates and mitochondrial respiratory activity under nutrient-excess conditions.
- THBS1 / TGF-β signaling — examined in relation to fibrosis-associated signaling markers in cardiac tissue models.
- Neuroinflammatory & oxidative-stress markers — examined in relation to microglial activation markers and oxidative stress indices in neuronal model systems.
Model Systems Studied
MOTS-C has been used as a test compound, and measured as an endogenous analyte, across a range of published preclinical and observational model systems. Refer to the cited literature for study designs, endpoints, and findings.
- Metabolic — high-fat-diet mouse models; insulin-resistant skeletal muscle cell lines; nutrient-excess skeletal muscle cell models.
- Cardiovascular — diabetic myocardial tissue models; hypertensive mouse models.
- Nervous system — rodent Aβ(1-42)- and LPS-induced cognitive-impairment models; LPS-stimulated neuronal cell cultures.
- In vitro cell signaling — cell-culture metabolic-stress and AMPK-activation assay systems.
- Human observational — serum and skeletal-muscle MOTS-C measurement cohorts (exercise, polycystic ovary syndrome, and metabolic-parameter studies).
Note: much of the human literature is observational (associational, not causal), and no controlled human clinical trials have been published; independent replication of preclinical findings remains limited.
Molecular & Technical Profile
C100H152N28O22S2 | MW 2174.57 g/mol | CAS 1901518-07-7 | Origin: mitochondrial-derived peptide (12S rRNA reading frame)
Storage, Reconstitution & Working Concentrations
Storage, reconstitution, and working-concentration values are general laboratory guidance for in vitro and animal research; always confirm against the lot-specific Certificate of Analysis.
Current Research Status
As of the time of this writing, MOTS-C has not been approved by the U.S. Food and Drug Administration (FDA) for any human therapeutic use. The available evidence base is primarily preclinical, derived from rodent and in vitro models, alongside observational human cohort data in which MOTS-C is measured as an endogenous analyte. Translation to human clinical contexts has not been established through controlled clinical trials, and the published literature notes unresolved pharmacokinetic questions and the context-dependency of measured outcomes. Ongoing research continues to characterize the compound's mechanistic profile and identify which experimental findings may have translational relevance.
Research FAQ
Is MOTS-C approved for human use?
No. MOTS-C has not been approved by the FDA for any human therapeutic use. The evidence base is preclinical (rodent and in vitro models) and observational, and the compound is supplied for laboratory research use only — not for human consumption.
What is MOTS-C's molecular formula?
A mitochondrial-derived peptide encoded within the mitochondrial genome — molecular formula C100H152N28O22S2, MW 2174.57 g/mol, CAS 1901518-07-7.
How is MOTS-C stored and reconstituted?
Store lyophilized at −20°C, protected from light (reported stable up to ~24 months). Reconstitute in sterile water or PBS (pH 7.4); store the reconstituted solution at 2–8°C for up to ~28 days and avoid repeated freeze–thaw.
What targets and model systems has MOTS-C been studied in?
Preclinical and observational work has examined AMPK signaling, nuclear gene regulation, glucose transport and insulin signaling, fatty acid oxidation, and TGF-β pathway activity, across high-fat-diet mouse models, skeletal muscle cell lines, cardiac and vascular models, rodent cognitive-impairment models, and human serum cohorts. Note the observational and single-model caveats noted above.
Selected References
- Lee et al. - Original characterization of MOTS-c as a mitochondrial-derived peptide; measured metabolic homeostasis markers and obesity resistance in mouse models - Cell Metab, 2015
- Bhatt et al. - Reviewed mitochondrial-derived peptides as a novel class of signaling microproteins; characterized MOTS-c sequence and expression across tissues - J Gerontol A Biol Sci Med Sci, 2017
- Kim et al. - Assessed MOTS-c nuclear translocation and AMPK-dependent gene regulation under metabolic stress conditions in cell culture models - Mol Cell, 2020
- Ming et al. - Measured MOTS-c effects on glucose transporter expression and AMPK phosphorylation in insulin-resistant skeletal muscle cell lines - Am J Transl Res, 2018
- Lu et al. - Measured fatty acid oxidation rates and mitochondrial respiration in MOTS-c-treated skeletal muscle cells under nutrient-excess conditions - Front Physiol, 2021
- Reynolds et al. - Measured MOTS-c serum concentrations before and after acute exercise protocols in human subjects; correlated with metabolic rate and substrate utilization markers - Aging (Albany NY), 2018
- Fuku et al. - Analyzed association between mitochondrial MOTS-c encoding variants and physical performance metrics in aging cohorts - J Gerontol A Biol Sci Med Sci, 2021
- Zempo et al. - Measured blood pressure regulation and vascular tone markers in MOTS-c-treated hypertensive mouse models; assessed endothelial function endpoints - J Hypertens, 2019
- Yin et al. - Measured memory performance and neuroinflammatory markers in rodent models of Abeta(1-42)- and LPS-induced cognitive impairment following peripheral MOTS-c analogue administration - ACS Chem Neurosci, 2021
- Yi et al. - Assessed MOTS-c effects on microglial activation markers and oxidative stress indices in LPS-stimulated neuronal cell culture models - Oxid Med Cell Longev, 2022
- Cobb et al. - Reviewed regulatory and translational status of mitochondrial-derived peptides; noted absence of human clinical trial data and unresolved pharmacokinetic profiles for MOTS-c - Pharmacol Ther, 2017
- Dulloo et al. - Reviewed limitations of exercise-mimetic peptide research including context-dependency of metabolic outcomes and challenges in translating rodent dosing to human equivalents - Obes Rev, 2023