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Mots-C

Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c

A 16-amino acid mitochondrial-derived peptide that regulates metabolic homeostasis, enhances insulin sensitivity, and promotes longevity.

Quick Stats
Studies 137
Trials 5
Formula C101H152N28O22S2
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Utility 4
pubmed Oct 19, 2024

MOTS-c modulates skeletal muscle function by directly binding and activating CK2.

Kumagai. Hiroshi H; Kim. Su-Jeong SJ; Miller. Brendan B; Zempo. Hirofumi H; Tanisawa. Kumpei K; Nats...

MOTS‑c is a tiny protein that can hook onto an enzyme called CK2 and turn it on in muscle, which helps keep muscles from shrinking and makes them take up more sugar. In mice, giving MOTS‑c stopped muscle loss and improved glucose use, but only when CK2 was active. A common human version of MOTS‑c (K14Q) doesn’t bind CK2 well and is linked to higher risk of muscle loss and type‑2 diabetes in men, suggesting genetics may affect how well the peptide works.

Utility 4
pubmed Jan 19, 2021

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.

Zempo. Hirofumi H; Kim. Su-Jeong SJ; Fuku. Noriyuki N; Nishida. Yuichiro Y; Higaki. Yasuki Y; Wan. J...

A common Asian mitochondrial DNA change (m.1382A>C) creates a slightly different version of the peptide MOTS‑c (K14Q). This version works less well at improving insulin sensitivity, so men who carry it are more likely to develop type‑2 diabetes, especially if they are not physically active. Regular exercise can offset some of this risk, and the normal MOTS‑c peptide still helps in animal studies, but the altered K14Q version does not.

Utility 3
pubmed May 2, 2023

Role of MOTS-c in the regulation of bone metabolism.

Yi. Xuejie X; Hu. Guangxuan G; Yang. Yang Y; Li. Jing J; Jin. Junjie J; Chang. Bo B

MOTS‑c is a tiny protein made by mitochondria that helps protect cells and manage energy. New research shows it can make bone‑building cells grow and turn into bone, while also slowing down the cells that break bone down. Exercise naturally raises MOTS‑c levels, but we still don’t know exactly how this works in bone. The review suggests MOTS‑c could become a target for preventing or treating bone‑related metabolic problems.

Utility 3
pubmed May 15, 2025

MOTS-c attenuates lung ischemia-reperfusion injury via MYH9-Dependent nuclear translocation and transcriptional activation of antioxidant genes.

Li. Xiangyu X; Zhan. Faliang F; Qiu. Guangfeng G; Lu. Peng P; Shen. Zihao Z; Qi. Yuanpu Y; Wu. Minch...

The study shows that the tiny protein MOTS‑c, which comes from mitochondria, can protect lung blood vessels from damage caused by loss of oxygen and then re‑oxygenation. It does this by hitching a ride with a protein called MYH9 into the cell nucleus, where it turns on antioxidant genes that fight harmful free radicals. Giving extra MOTS‑c to rats reduced lung injury, inflammation and death, and changes in blood MOTS‑c levels after heart‑lung surgery predicted who would get severe lung problems.

Utility 3
pubmed Jun 4, 2025

MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway.

Zhang. Wenlong W; Li. Shengpeng S; Zhang. Yanli Y; Wu. Yaxian Y; Chen. Dan D; Pang. Qingfeng Q; Han....

A small protein called MOTS‑c is found at lower levels in people with asthma. In mouse and cell experiments, giving extra MOTS‑c protected lung cells from damage caused by allergens, reduced inflammation and oxidative stress, and kept the airway barrier intact by activating the Nrf2 pathway that prevents cell death. These results suggest MOTS‑c could be a future therapy for allergic asthma, but it’s still early‑stage research.

Utility 3
pubmed Jun 30, 2025

Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart.

Pham. Toan T; Taberner. Andrew A; Hickey. Anthony A; Han. June-Chiew JC

In a rat model of type‑2 diabetes, daily injections of the mitochondrial peptide MOTS‑c (15 mg per kg) for three weeks lowered blood sugar, reduced heart enlargement, and boosted the heart’s ability to produce energy, although it also raised some reactive oxygen species. These results hint that MOTS‑c could help fix the energy problems seen in diabetic hearts, but the work is still early and done in animals.

Utility 3
pubmed Aug 19, 2024

Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane.

Jia. Hong H; Zhou. Lyu-Chen LC; Chen. Yong-Feng YF; Zhang. Wei W; Qi. Wei W; Wang. Peng P; Huang. Xi...

MOTS‑c is a tiny protein made by mitochondria that helps cells fix damaged outer membranes by teaming up with a repair protein called TRIM72. Moderate‑intensity exercise raises your body’s MOTS‑c levels, improves membrane repair, and protects heart tissue after injury. In lab tests, MOTS‑c moves TRIM72 to the wound site and also works with membrane lipids to fuse repair vesicles, but it doesn’t fix membranes on its own without TRIM72.

Utility 3
pubmed Jan 11, 2024

The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression.

Lu. Huanyu H; Fan. Linni L; Zhang. Wenli W; Chen. Guo G; Xiang. An A; Wang. Li L; Lu. Zifan Z; Zhai....

A study found that the naturally‑made peptide MOTS‑c can protect the liver from fatty‑liver disease (NASH) in animal models by boosting mitochondria, cutting cell death, inflammation and scarring. It works by binding to the anti‑death protein Bcl‑2 and keeping it stable. While promising for liver health, the work is still in mice and no human dosing or safety info is available yet.

Utility 3
pubmed Sep 1, 2023

The relationship of circulating MOTS-c level with liver fibrosis and metabolic components in patients with metabolic dysfunction-associated fatty liver disease.

Kirik. A A; Dogru. T T; Yanik. B B; Sen. H H; Eroglu. M M; Baykan. O O; Bozyel. E A EA; Ergene. A A;...

People with fatty liver disease (MAFLD) and metabolic syndrome have lower levels of the mitochondrial peptide MOTS‑c in their blood, and the lower the MOTS‑c, the worse their liver fibrosis scores and metabolic health markers tend to be.

Utility 3
pubmed Oct 1, 2025

MOTS-c attenuates mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via an Nrf2-Dependent Mechanism.

Li. Kechi K; Yang. Tao T; Chen. Feiyu F; Lou. Chao C; Chen. Yanlin Y; Chen. Zhenzhong Z; Ye. Lin L;...

A study found that giving the mitochondrial peptide MOTS‑c to cells and mice with osteoarthritis helped fix broken mitochondria, cut down harmful inflammation and cell death, and slowed joint cartilage damage. The benefits came from activating the body’s antioxidant Nrf2 pathway, which in turn calmed down a chain of inflammatory signals.

Utility 3
pubmed May 17, 2024

The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism.

Zhang. Yanli Y; Huang. Jianfeng J; Zhang. Yaru Y; Jiang. Fengjuan F; Li. Shengpeng S; He. Shuai S; S...

In mice, the tiny protein MOTS‑c helped protect lung cells from the damage caused by high‑dose radiation, mainly by boosting a cellular defense system called Nrf2 that keeps mitochondria healthy. The benefit disappeared when Nrf2 was missing, showing the peptide works through that pathway.

Utility 3
pubmed Jan 3, 2024

Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Kumagai. Hiroshi H; Kim. Su-Jeong SJ; Miller. Brendan B; Natsume. Toshiharu T; Wan. Junxiang J; Kuma...

In mice, giving the mitochondrial peptide MOTS‑c (about 15 mg per kg each day) cut muscle loss from being immobilized by two‑thirds, lowered inflammation, and stopped fat from building up inside the muscle, likely by tweaking genes that control fat creation.

Utility 3
pubmed Jun 28, 2023

The Mitochondrial-Derived Peptide (MOTS-c) Interacted with Nrf2 to Defend the Antioxidant System to Protect Dopaminergic Neurons Against Rotenone Exposure.

Xiao. Jingsong J; Zhang. Qifu Q; Shan. Yaohui Y; Ye. Feng F; Zhang. Xi X; Cheng. Jin J; Wang. Xiaoga...

The study shows that giving the tiny mitochondrial peptide MOTS‑c to cells and rats helps protect dopamine‑producing brain cells from damage caused by the toxin rotenone, mainly by boosting the body’s antioxidant defenses through the Nrf2 pathway. While the work is still in early lab and animal stages, it hints that MOTS‑c might be useful for neuro‑protection, but real‑world dosing and safety in people are not yet known.

Utility 3
pubmed Oct 11, 2025

MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment.

Fang. Tingting T; Han. June-Chiew JC; Taberner. Andrew A; Pham. Toan T

The review explains that the tiny protein MOTS‑c, made by mitochondria, is often low in people with type‑2 diabetes and may contribute to the disease and heart problems. Lab studies in animals show that giving extra MOTS‑c can improve blood sugar control, boost metabolism, and protect the heart, and researchers have tried several doses and timing schedules. However, there are no human trials yet, so the information is mostly a guide for future experiments rather than a ready‑to‑use supplement plan.

Utility 3
pubmed Feb 25, 2025

Reduced serum levels of mitochondria-derived peptide MOTS-c in patients with obstructive sleep apnea.

Luo. Zhuoding Z; Ji. Rui R; Ye. Renjing R; Shi. Yawen Y; Pang. Qingfeng Q; Yin. Min M

The study found that people with obstructive sleep apnea (OSA) have lower levels of a mitochondrial peptide called MOTS‑c, and the worse the sleep apnea or the higher the body‑mass index, the lower the MOTS‑c. This link suggests MOTS‑c might play a role in the metabolic problems seen with OSA and could become a target for future treatments.

Utility 3
pubmed Jul 17, 2025

Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization.

Elhusseiny. Rabie R; Ihsan. Mohammed M; Labidi. Mariem M; Alhammoud. Marine M; Mtibaa. Khouloud K; N...

In a small study of active men, applying heat to a leg that was immobilized for two weeks raised the blood level of the mitochondrial peptide MOTS‑C and lowered the muscle level of another mitokine, FGF21, but it didn’t stop the muscle from getting smaller. This shows heat can change these signaling molecules in a way similar to exercise, though it isn’t enough by itself to protect against muscle loss.

Utility 3
pubmed Apr 16, 2024

An 8-Week study on the effects of high and Moderate-Intensity interval exercises on mitochondrial MOTS-C changes and their relation to metabolic markers in male diabetic sand rats.

Parseh. Sahar S; Shakerian. Saeid S; Reza Tabandeh. Mohammad M; Habibi. Abdolhamid A

In diabetic sand rats, doing moderate‑intensity interval workouts for eight weeks boosted the mitochondrial peptide MOTS‑C, as well as other metabolism‑related proteins, more than high‑intensity training, and it lowered insulin resistance. This suggests that, at least in this animal model, a less intense but still interval‑based exercise routine may be better for improving metabolic health.

Utility 3
pubmed Nov 1, 2024

The Human Mitochondrial Genome Encodes for an Interferon-Responsive Host Defense Peptide.

Rice. M C MC; Imun. M M; Jung. S W SW; Park. C Y CY; Kim. J S JS; Lai. R W RW; Barr. C R CR; Son. J...

MOTS‑c is a tiny protein made by mitochondria that can kill bacteria and help immune cells work better, especially after signals like interferon or bacterial components. It moves into the cell nucleus and changes how macrophages behave, boosting their ability to clear infections and shifting their metabolism. While this shows MOTS‑c could be a natural way to support immunity and metabolic health, the study is early‑stage and doesn’t give dosing or real‑world usage guidelines.

Utility 3
pubmed Aug 19, 2025

Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging.

Tero-Vescan. Amelia A; Degens. Hans H; Matsakas. Antonios A; Ștefănescu. Ruxandra R; &#x...

The paper explains how exercise makes muscles and fat talk to each other using signaling proteins, which keeps the body flexible in using carbs or fats for energy. It highlights a tiny peptide called MOTS‑c that can mimic some exercise benefits, and mentions that omega‑3s or low‑dose aspirin might help protect mitochondria. For biohackers, the take‑away is that regular training plus possibly experimenting with MOTS‑c and anti‑inflammatory supplements could boost metabolism and slow age‑related decline.