MOTS-c
Mitochondrial ORF of the twelve S rRNA type-c
A mitochondria-encoded peptide that acts as a metabolic signal to the rest of the body, studied for insulin sensitivity and exercise capacity.
Last reviewed · 2 references
How it works
MOTS-c is encoded not in the nucleus but in mitochondrial DNA — one of a small family of peptides that let mitochondria signal outward to the cell and the organism. It activates AMPK, shifts folate-methionine metabolism, and can translocate to the nucleus under metabolic stress to regulate stress-adaptive genes. Its levels decline with age.
Animal studies only. Findings come from rodent or in-vitro models. Animal results frequently fail to replicate in people.
What the research reports
- Improved insulin sensitivity and prevented diet-induced obesity in mice
- Increased exercise capacity in aged mice
- Higher circulating levels associated with metabolic health in human observational data
- AMPK activation, the same pathway targeted by metformin and exercise
What it has not been shown to do
- No completed randomised human trial of exogenous MOTS-c
- No demonstrated effect on mood or cognition in humans
- The mood connection is entirely inferential, via the mitochondrial theory of depression
Dosing reference
No established human dose. Animal studies use weight-scaled amounts that do not translate directly.
Calculate my dose for MOTS-c- Routes studied
- Subcutaneous
- Half-life
- Short in circulation; not well characterised in humans
- Cycle length in the literature
- Not established
Working out a draw volume from a vial? Use the free reconstitution calculator.
Side effects and contraindications
Reported side effects
- Injection-site reaction
- Otherwise uncharacterised in humans
Do not use if
- Pregnancy and breastfeeding
- Diabetes managed with insulin or sulfonylureas — an AMPK activator can compound hypoglycaemia risk
The practice that shares the mechanism
MOTS-c is essentially an exercise-mimetic signal. Exercise, fasting and cold exposure activate the same AMPK pathway and have decades of human safety behind them. If mitochondrial function is the target, the practices are not the consolation prize — they are the better-evidenced intervention.
What amplifies it
- Zone-2 cardio drives mitochondrial biogenesis directly
- Time-restricted eating activates the same AMPK signal
- Sleep debt measurably impairs mitochondrial function and works against everything here
Mechanism hubs
Common questions
- Indirectly, through energy. A growing body of research links depressive symptoms to impaired mitochondrial function — the brain is roughly two percent of body mass and consumes around twenty percent of resting energy, and neurotransmitter synthesis is ATP-expensive. MOTS-c improves mitochondrial signalling in animals. Nobody has shown that this improves mood in a person.
- For the AMPK pathway specifically, exercise has vastly more human evidence than exogenous MOTS-c — and MOTS-c is itself released in response to exercise. That is an uncomfortable finding for the compound but an honest one.
Sources & evidence notes
Findings come from rodent or in-vitro models. Animal results frequently fail to replicate in people.
Confidence score 7/100
Preliminary
Mechanism only. Nothing here establishes that a person would feel anything.
- 1.
Cell Metabolism, 2015 · Source (opens in a new tab)
In vitroLimited gradeCells or tissue in a dish. Tells you about mechanism, not about outcomes. - 2.
Nature Communications, 2021 · Source (opens in a new tab)
In vitroLimited gradeCells or tissue in a dish. Tells you about mechanism, not about outcomes.