MOTS-c
Mitochondrially encoded peptide
A 16 amino acid peptide whose blueprint lies not in the cell nucleus but in the mitochondria's own genome. Since its discovery in 2015, a model for the question of how mitochondria help steer the metabolism of the whole cell.
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
At a glance
- 01
A gene inside the mitochondrion
Mitochondria carry their own, very small genome. MOTS-c is encoded in a short reading frame within the 12S rRNA gene, a place where nobody expected a peptide for a long time. It belongs to the young family of mitochondrial-derived peptides.
- 02
A signal to the nucleus
Under metabolic stress, MOTS-c enters the nucleus in cell models and influences the activity of nuclear genes there. For research this is a rare case of the mitochondrion actively communicating with the nucleus.
- 03
Triggered by exercise
In young men, endogenous MOTS-c rose about twelvefold in skeletal muscle and about one and a half times in blood after a single exercise session. This makes the peptide a tool for studying the metabolic response to physical activity.
Fields of research
- Mitochondrial signalling
- AMPK and energy metabolism
- Insulin sensitivity in animal models
- Skeletal muscle and physical capacity
- Ageing research
What it is
MOTS-c stands for “mitochondrial open reading frame of the 12S rRNA-c”. The name describes its origin: the peptide is encoded in the mitochondrial genome, in a short section of the gene for the ribosomal 12S RNA. It was described in 2015 by a research group at the University of Southern California. The synthetic peptide matches its natural counterpart in sequence and length.
Mitochondria are classically seen as the power plants of the cell. MOTS-c is one of the peptides showing that they also produce messengers with which they influence the rest of the cell and possibly the whole organism.
What makes it special
Most known peptide hormones are encoded in the nucleus. MOTS-c comes from a second, much smaller genome and was found in a region that until then was considered a blueprint for RNA only. This opened the question of how many such small reading frames in the mitochondrial genome remain undiscovered.
Then there is the mechanism: in cell models, MOTS-c interferes with the folate cycle, leading to accumulation of the metabolic intermediate AICAR and activation of the energy-sensing kinase AMPK. Later work showed that under stress the peptide moves into the nucleus and helps regulate gene expression there.
What the studies say
Lee et al. (2015) describe the discovery and the first animal experiments. Skeletal muscle emerged as the main target organ. In mice, MOTS-c prevented weight gain and insulin resistance induced by a high-fat diet, as well as age-related insulin resistance.
Reynolds et al. (2021) studied young, middle-aged and old mice. MOTS-c improved physical performance in all age groups. Intermittent treatment started only late in life improved grip strength, gait and running capacity; for lifespan there was a trend that remained statistically borderline. In humans the authors measured the endogenous peptide: after exercise it rose markedly in muscle and blood.
State of evidence
Preclinical: solid, but still young. Clinical: no controlled studies. The findings come from cell culture and mouse models, largely from one research environment. The human data only describe how the endogenous peptide behaves, not the effect of administered MOTS-c.
Research status
MOTS-c is not approved as a medicine in any country. The World Anti-Doping Agency lists it by name on the prohibited list (category S4, AMPK activators). PURA LABS supplies MOTS-c for research use only, not for human or animal use.
Selected literature
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistanceFirst description of MOTS-c, a 16 amino acid peptide from a reading frame of the mitochondrial 12S rRNA gene. In cells it inhibits the folate cycle and activates AMPK; in mice it prevented diet-induced obesity and insulin resistance.
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasisMOTS-c improved physical performance in young, middle-aged and old mice, even when treatment began late in life. In humans, the endogenous peptide rose in muscle and blood after exercise.
Current batch
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