Peptides >MOTS-c


The Mitochondrial-Derived Peptide MOTS-c enhances metabolic balance and longevity. It enhances exercise performance, lowers obesity, mitigates insulin resistance, and addresses conditions like osteoporosis.

This PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused or mislabled as a drug, food or cosmetic.


1. MOTS-c Overview


2. Structure of MOTS-c


3. Research on MOTS-c

MOTS-c Overview

MOTS-c is a short peptide encoded in the mitochondrial genome and is part of the mitochondrial-derived peptides (MDPs) group. Recent discoveries have revealed that MDPs act as bioactive hormones involved in mitochondrial communication and energy regulation. Initially associated solely with mitochondria, further research has unveiled their presence in the cell nucleus and their circulation in the bloodstream, exerting systemic effects. MOTS-c, a newly identified MDP, has demonstrated its significance in metabolism, weight regulation, exercise capacity, longevity, and processes leading to diseases like osteoporosis. It has been detected both in cell nuclei and in the general circulation, establishing its status as a natural hormone. In the past five years, MOTS-c has garnered significant attention in the field of research due to its therapeutic potential. 

Structure of MOTS-c

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 SID: 255386757

CAS Number: 1627580-64-6

Synonyms: Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1


Research on MOTS-c

Muscle Metabolism Research in mice suggests that MOTS-c can reverse age-related insulin resistance in muscles, enhancing glucose uptake by skeletal muscles. This effect is achieved by improving the response of skeletal muscles to AMPK activation, leading to increased expression of glucose transporters. Notably, this mechanism operates independently of the insulin pathway, providing an alternative method for boosting glucose uptake in muscles when insulin is insufficient. The overall outcome is improved muscle function, enhanced muscle growth, and reduced functional insulin resistance.

Fat Metabolism Studies in mice have indicated that low estrogen levels can lead to increased fat accumulation and abnormal adipose tissue function, elevating the risk of insulin resistance and diabetes. Supplementing mice with MOTS-c, however, enhances brown fat function and reduces adipose tissue accumulation. Additionally, MOTS-c appears to prevent adipose tissue dysfunction and inflammation, which are often precursors to insulin resistance.

MOTS-c’s influence on fat metabolism is partially mediated through the activation of the AMPK pathway, a well-established pathway that promotes the uptake and metabolism of both glucose and fatty acids in cells during periods of low energy levels. This pathway is also activated by ketogenic diets, such as the Atkins diet, which encourage fat metabolism while preserving lean body mass. MOTS-c specifically targets the methionine-folate cycle, increases AICAR levels, and activates AMPK.

Recent research suggests that MOTS-c can translocate from mitochondria to the nucleus, where it can affect the expression of nuclear genes. After metabolic stress, MOTS-c has been shown to regulate nuclear genes involved in glucose regulation and antioxidant responses.

MOTS-C Structure MOTS-c exerts its effects in both the mitochondria and the nucleus.

Evidence from studies in mice suggests that MOTS-c, particularly in the context of obesity, plays a crucial role in regulating sphingolipid, monoacylglycerol, and dicarboxylate metabolism. By downregulating these pathways and increasing beta-oxidation, MOTS-c appears to prevent the accumulation of fat. Some of these effects are likely mediated through MOTS-c’s actions in the nucleus. Research on MOTS-c has given rise to a new hypothesis concerning fat deposition and insulin resistance, offering potential insights into the pathophysiology of obesity and diabetes. Dysregulation of fat metabolism in mitochondria may lead to reduced fat oxidation, prompting elevated insulin levels in an attempt to clear lipids from the bloodstream, ultimately resulting in increased fat deposition and insulin resistance.

Supplementation of MOTS-c in rats has been shown to prevent mitochondrial dysfunction and fat accumulation, even in the presence of a high-fat diet.

Insulin Sensitivity Research assessing MOTS-c levels in individuals with varying insulin sensitivity has revealed that the protein is associated with insulin sensitivity primarily in lean individuals. This suggests that MOTS-c may play a role in the development of insulin insensitivity rather than its maintenance. Scientists speculate that monitoring MOTS-c levels in lean, pre-diabetic individuals could serve as an early indicator of potential insulin resistance. Supplementation with MOTS-c in this population may help delay the onset of insulin resistance and the development of diabetes. Although promising results have been observed in mouse studies, further research is required to fully understand MOTS-c’s impact on insulin regulation.

Osteoporosis MOTS-c appears to be involved in the synthesis of type I collagen by osteoblasts in bone. Research in osteoblast cell lines suggests that MOTS-c regulates the TGF-beta/SMAD pathway, which is responsible for osteoblast health and survival. By promoting osteoblast survival, MOTS-c enhances the synthesis of type I collagen, consequently improving bone strength and integrity.

Further research in osteoporosis has shown that MOTS-c promotes the differentiation of bone marrow stem cells through the same TGF-beta/SMAD pathway, leading to increased osteogenesis (formation of new bone). Thus, MOTS-c not only protects osteoblasts and supports their survival but also promotes their development from stem cells.

Longevity Studies on MOTS-c have identified a specific genetic variation in the peptide associated with longevity in certain populations, such as the Japanese. This genetic change involves substituting a glutamate residue for the lysine normally found at position 14 of the protein. While the functional implications of this change are not yet fully understood, it is exclusive to individuals of Northeast Asian ancestry and is believed to contribute to their exceptional longevity.

According to Dr. Changhan David Lee, a researcher at the School of Gerontology at USC Leonard Davis, mitochondria are crucial for extending both lifespan and healthspan in humans. Mitochondria are strongly implicated in aging and age-related diseases. Previously, dietary restriction was the primary method to influence mitochondrial function and longevity. Peptides like MOTS-c, however, may offer a more direct way to impact mitochondrial function.

Heart Health Research involving patients undergoing coronary angiography has revealed that individuals with lower levels of MOTS-c in their blood exhibit higher levels of endothelial cell dysfunction. Endothelial cells, lining the interior of blood vessels, play a crucial role in regulating blood pressure, blood clotting, and plaque formation. Studies in rats suggest that while MOTS-c doesn’t directly affect blood vessel responsiveness, it does sensitize endothelial cells to the effects of other signaling molecules, like acetylcholine. Supplementation with MOTS-c has been shown to enhance endothelial function and improve the function of microvascular and epicardial blood vessels.

MOTS-c is not the only mitochondria-derived peptide (MDP) affecting heart health. Research suggests that at least three MDPs play roles in protecting cardiac cells from stress and inflammation, potentially playing a role in cardiovascular disease development and reperfusion injury.

MOTS-c has demonstrated minimal side effects, low oral availability, and excellent subcutaneous bioavailability in mice. However, the dosage in mice does not scale directly to humans. MOTS-c available for purchase at Peptide Sciences is intended for educational and scientific research purposes only and is not for human consumption. It should only be obtained by licensed researchers.

MOTS-c has effects in both the mitochondria and the nucleus.
MOTS-c supplementation in rats prevents mitochondrial dysfunction and prevents the accumulation of fat even in the setting of a high-fat diet.

Article Author

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.


The product information featured on this website pertains exclusively to in-vitro studies. In-vitro studies, also known as ‘in glass’ studies, are conducted outside of living organisms. It’s important to emphasize that these products do not constitute medicines or drugs and have not received FDA approval for the prevention, treatment, or cure of any medical conditions, ailments, or diseases. It is crucial to note that the introduction of these products into the bodies of humans or animals is strictly prohibited by law.