MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c)

Mitochondrial-Derived Peptide · Metabolic Regulator

Overview

MOTS-c is a mitochondrial-derived peptide that operates as a mitohormone through the Folate-AICAR-AMPK pathway. Under metabolic stress, it translocates to the nucleus to bind stress-response transcription factors (NRF2, ATF1/ATF7), regulating genes involved in metabolism and cellular adaptation.

Inhibits the folate cycle leading to AMPK activation. Under metabolic stress, translocates to nucleus to bind stress-response transcription factors, regulating genes involved in metabolism, insulin sensitivity, and cellular adaptation.

Improves insulin sensitivity by ~30% in animal studies through AMPK activation.

Restores metabolic function via insulin receptor sensitization.

Promotes fatty acid oxidation despite identical caloric intake.

Reverses age-dependent physical decline in animal models.

Mechanism

Improves insulin sensitivity by ~30% in animal studies through AMPK activation.

Research areas

MOTS-c is a mitochondrial-derived peptide that operates as a mitohormone through the Folate-AICAR-AMPK pathway. Under metabolic stress, it translocates to the nucleus to bind stress-response transcription factors (NRF2, ATF1/ATF7), regulating genes involved in metabolism and cellular adaptation.
Inhibits the folate cycle leading to AMPK activation. Under metabolic stress, translocates to nucleus to bind stress-response transcription factors, regulating genes involved in metabolism, insulin sensitivity, and cellular adaptation.
Improves insulin sensitivity by ~30% in animal studies through AMPK activation.
Restores metabolic function via insulin receptor sensitization.
Promotes fatty acid oxidation despite identical caloric intake.
Reverses age-dependent physical decline in animal models.
Enhances mitochondrial function via PGC-1α activation.
6.4% median lifespan extension observed in mice studies.
12-15% improvement in running performance from single dose in studies.
Exercise induced 11.9-fold increase in skeletal muscle MOTS-c.
Supports muscle recovery and adaptation to exercise.

Research notes

Generally well-tolerated in animal studies with minimal side effects
Mild injection site reactions (redness, swelling)
Severe allergic reactions or anaphylaxis
Recurrent hypoglycemia (<50 mg/dL)
Persistent severe injection site reactions
Unexplained weight loss >10% of baseline
Pregnancy or breastfeeding
WADA prohibited substance (banned for athletic competition)
Limited long-term human safety data

AXIOM catalogue

MOTS-C — research-use catalogue record with strengths and available batch details where listed.

References

FAQs

How does MOTS-c help with insulin resistance?

MOTS-c activates AMPK, a cellular energy sensor that improves insulin sensitivity by approximately 30% in animal studies. It works through the Folate-AICAR-AMPK pathway, enhancing glucose uptake in muscle tissue. This addresses metabolic dysfunction at the mitochondrial level.

Does MOTS-c work for weight loss?

Indirectly. MOTS-c promotes fatty acid oxidation despite identical caloric intake, improving metabolic flexibility. Combined with exercise and diet, it enhances the body's ability to burn fat for fuel. It's not a direct weight-loss peptide like GLP-1 agonists, but supports metabolic health.

Can MOTS-c extend lifespan in humans?

Unknown in humans. Animal studies show 6.4% median lifespan extension in mice. MOTS-c clearly supports healthspan and metabolic optimization, but human longevity data doesn't exist. It's a longevity-supporting compound, not a proven life-extension drug.

Should I take MOTS-c before or after exercise?

Morning before exercise is optimal. MOTS-c activates AMPK within 30 minutes, enhancing exercise performance by 12-15% in studies. Post-workout benefits are also seen for recovery. However, pre-exercise timing maximizes the performance enhancement during the workout itself.