MOTS-C

What Is MOTS-c ?

MOTS-c is a mitochondrial-derived peptide (MDP) made up of 16 amino acids. It plays a key role in regulating how cells handle metabolism. This peptide is produced inside mitochondria and helps balance cellular energy by affecting pathways related to glucose use, insulin response, and how cells deal with stress. MOTS-c moves to the cell’s nucleus, where it influences genes involved in creating new mitochondria and managing metabolism, especially during times of metabolic stress. Studies show that it can boost exercise performance, reduce obesity and insulin resistance, and help with conditions like osteoporosis, as well as ease metabolic disorders and diseases linked to aging.
The mitochondrial-derived peptide MOTS-c supports metabolic balance and longer life. It improves exercise ability, cuts down on obesity and insulin resistance, and aids in other health issues like osteoporosis.

Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Molecular Formula: C101H152N28O22S2
Molecular Weight: 2174.64 g/mol
PubChem CID: 146675088
CAS Number: 1627580-64-6
Synonyms: Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1

Muscle Metabolism
Studies in mice suggest that MOTS-c can reverse insulin resistance in muscles that comes with aging, which helps muscles take in more glucose. It does this by boosting the muscle’s response to AMPK activation, leading to more glucose transporters. This process works without relying on insulin, so it provides another way to increase glucose uptake when insulin isn’t working well or there’s not enough of it. Overall, this leads to better muscle performance, stronger muscle growth, and less effective insulin resistance.
Fat Metabolism
Research in mice shows that low estrogen levels cause more fat buildup and problems in normal fat tissue. This raises the risk of insulin resistance and eventually diabetes. However, adding MOTS-c to these mice boosts brown fat activity and reduces fat accumulation. The peptide also seems to prevent fat tissue problems and the inflammation that often comes before insulin resistance.
At least some of MOTS-c’s effects on fat metabolism come from activating the AMPK pathway. This pathway kicks in when cell energy is low, helping cells take in glucose and fatty acids for energy. It’s the same pathway activated in low-carb diets like the Atkins diet, which encourage fat burning while preserving muscle. MOTS-c affects the methionine-folate cycle, raises AICAR levels, and turns on AMPK.
New studies indicate that MOTS-c can leave the mitochondria and go to the nucleus, where it influences gene expression. After metabolic stress, MOTS-c helps regulate nuclear genes tied to limiting glucose and responding to antioxidants.
Evidence from mice shows that MOTS-c, especially in obesity, regulates metabolism of sphingolipids, monoacylglycerols, and dicarboxylates. By slowing these pathways and boosting beta-oxidation, MOTS-c helps prevent fat buildup. Some of these effects likely happen through its actions in the nucleus. Research on MOTS-c has sparked a new idea about fat storage and insulin resistance that’s gaining support among scientists. It could lead to fresh ways to treat obesity and diabetes. The theory is that issues in mitochondrial fat metabolism reduce fat burning, leading to more fat in the blood. This forces the body to raise insulin to clear the fats, resulting in more fat storage and adaptation to high insulin levels, which causes resistance.
Insulin Sensitivity
Studies measuring MOTS-c levels in people who are insulin sensitive versus resistant show that the peptide links to insulin sensitivity only in lean people. In short, MOTS-c seems key in starting insulin insensitivity but not in keeping it going. Researchers think the peptide could help monitor lean people at risk for diabetes, with changes in MOTS-c levels serving as an early alert for potential issues. Adding MOTS-c might prevent insulin resistance and diabetes. Mouse studies look promising so far, but more research is needed to fully grasp its role in insulin control.
Osteoporosis
MOTS-c seems to help osteoblasts in bone make type I collagen. In lab studies with osteoblast cells, MOTS-c regulates the TGF-beta/SMAD pathway, which supports osteoblast health and survival. By helping osteoblasts live longer, MOTS-c boosts type I collagen production, strengthening bones.
More osteoporosis research shows MOTS-c encourages bone marrow stem cells to turn into osteoblasts via the same TGF-beta/SMAD pathway. This directly increases new bone formation. So, MOTS-c not only protects and supports existing osteoblasts but also promotes their creation from stem cells.
Longevity
Studies on MOTS-c have found a specific gene change linked to longer life in groups like the Japanese. This change swaps a glutamate for the usual lysine at position 14 in the peptide. It’s unclear how this alters the peptide’s function, but it’s likely since glutamate and lysine have very different traits, affecting the peptide’s shape and role. More studies are needed, but this change appears only in people with Northeast Asian roots and may contribute to their notable long lifespans.
According to Dr. Changhan David Lee, a researcher at USC Leonard Davis School of Gerontology, mitochondrial biology is crucial for extending both lifespan and healthy years in humans. As the main metabolic powerhouse, mitochondria are deeply tied to aging and related diseases. Until now, cutting calories was the main way to influence mitochondrial function and longevity. But peptides like MOTS-c might allow direct, stronger impacts on mitochondria.
Heart Health
Research on people getting coronary angiography shows that lower blood levels of MOTS-c link to more dysfunction in endothelial cells. These cells line blood vessels and help control blood pressure, clotting, and plaque buildup. Rat studies suggest MOTS-c doesn’t directly change blood vessel reactions but makes endothelial cells more responsive to signals like acetylcholine. Giving rats MOTS-c improves endothelial function and enhances small and large blood vessel performance.
MOTS-c isn’t the only MDP affecting heart health. At least three MDPs help shield heart cells from stress and inflammation. There’s evidence that MDP imbalances play a role in heart disease development. These peptides might even factor into damage from restoring blood flow and, as mentioned, endothelial function.