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Home/Compounds/MOTS-c
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MOTS-c

Also known as: Mitochondrial ORF of the 12S rRNA Type-c

Mitochondrial-derived peptide that improves metabolic function and exercise capacity.

C
Grade C
Animal studies only
Human studies27
PubMed citations30
Typical dose5 mg – 15 mg
Routesubcutaneous
Regulatory (US)Compounding legal
Last verified2 days ago
TL;DR · 30-second summary
  • Improves insulin sensitivity
  • Mimics exercise at cellular level (AMPK activation)
  • Declines with age (potential biomarker)
  • May enhance exercise performance

Mechanism of action

Encoded in mitochondrial genome, released during stress. Activates AMPK pathway, improves glucose uptake, enhances insulin sensitivity, and mimics exercise benefits.

Evidence summary

27
Human studies
30
PubMed citations
4
Clinical trials
C
Evidence grade

Early human studies show improved metabolic parameters. Levels decline with age. Exercise and metformin increase endogenous MOTS-c.

Dosing protocols

Educational information only. Consult a licensed provider before using any peptide.
Dose range
5 mg – 15 mg

5-15mg 3-5x weekly. Often used 5mg daily for metabolic support.

Administration routes
subcutaneous

Side effects & safety

Reported side effects
Generally well toleratedLimited safety dataPossible injection site reactions
Contraindications
  • Unknown - limited data

Interactions

No documented drug interactions on file.

Regulatory status

United States
Not FDA approved

Not FDA approved. Research peptide.

Compounding
Permitted

Available through compounding pharmacies with valid prescription.

Regulatory data last verified 4/17/2026

Citations

PMID 41468174Liu Z, Shen Z et al. · Muscle-Targeted Nanocomposite Therapy Alleviates Age-Related Sarcopenia via Antioxidant and Metabolic Reprogramming.ACS nano (2026)HumanPMID 39706498Feng Y, Rao Z et al. · Endurance training enhances skeletal muscle mitochondrial respiration by promoting MOTS-c secretion.Free radical biology & medicine (2025)HumanPMID 40496439Heldens A, Antwi M et al. · Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD.JHEP reports : innovation in hepatology (2025)HumanPMID 40005438Zicarelli M, Greco M et al. · MOTS-c Levels and Sarcopenia Risk in Chronic Peritoneal Dialysis Patients: A Pilot Study.Medicina (Kaunas, Lithuania) (2025)HumanPMID 39876762Leciejewska N, Pruszyńska-Oszmałek E et al. · MOTS-c Impact on Muscle Cell Differentiation and Metabolism Across Fiber Types.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (2025)PMID 39616938Fu Y, Tang M et al. · MOTS-c regulates the ROS/TXNIP/NLRP3 pathway to alleviate diabetic cardiomyopathy.Biochemical and biophysical research communications (2024)PMID 38160808Kal S, Mahata S et al. · Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.Peptides (2024)HumanPMID 34896254Gong Z, Goetzman E et al. · Cardio-protective role of Humanin in myocardial ischemia-reperfusion.Biochimica et biophysica acta. General subjects (2024)HumanPMID 39321430Yin Y, Li Y et al. · Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)HumanPMID 38430258Bień J, Pruszyńska-Oszmałek E et al. · MOTS-c regulates pancreatic alpha and beta cell functions in vitro.Histochemistry and cell biology (2024)HumanPMID 34520826Woodhead JST, Merry TL · Mitochondrial-derived peptides and exercise.Biochimica et biophysica acta. General subjects (2024)HumanPMID 38170165Kumagai H, Kim SJ et al. · Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.American journal of physiology. Endocrinology and metabolism (2024)HumanPMID 38008175Li Y, Li Z et al. · Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.Journal of advanced research (2024)HumanPMID 38462167Ozturk Öztürk DA, Erden Y et al. · Central MOTS-c infusion affects reproductive hormones in obese and non-obese rats.Neuroscience letters (2024)PMID 36687680Wang M, Wang G et al. · MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats.Frontiers in nutrition (2023)HumanPMID 36490309Cuyàs E, Verdura S et al. · Circulating levels of MOTS-c in patients with breast cancer treated with metformin.Aging (2023)HumanPMID 37437978Dabravolski SA · Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases.Advances in protein chemistry and structural biology (2023)HumanPMID 34471251Goetzl EJ, Wolkowitz OM et al. · Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder.Molecular psychiatry (2022)HumanPMID 35656563Yoon TK, Lee CH et al. · Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c).Diabetes & metabolism journal (2022)HumanPMID 34798268Yin Y, Pan Y et al. · The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.Pharmacological research (2022)Human

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