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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 3
pubmed Aug 19, 2024

The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis.

Zhou. Qian Q; Yin. Shao S; Lei. Xingxing X; Tian. Yuting Y; Lin. Dajun D; Wang. Li L; Chen. Qiu Q

The study pooled data from several small trials and found that people with type‑2 diabetes have lower blood levels of the mitochondrial peptide MOTS‑c, while people who are obese (especially with a BMI over 28) tend to have higher levels. MOTS‑c also showed a modest positive link with total and LDL cholesterol. These patterns suggest MOTS‑c could act as a biomarker for metabolic health, but the research is still early and the tests aren’t widely available for everyday use.

Utility 3
pubmed Mar 16, 2023

The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats.

Li. Can C; Li. Nan N; Zhang. Ziyi Z; Song. Yu Y; Li. Jialin J; Wang. Zhe Z; Bo. Hai H; Zhang. Yong Y

In rats fed a high‑fat diet, the slow‑twitch (endurance) muscle stayed more insulin‑sensitive than the fast‑twitch (power) muscle. This protection was linked to higher activity of the mitochondrial unfolded protein response (UPRmt) and more of the peptide MOTS‑c in the slow‑twitch muscle, which kept its mitochondria working well. Fast‑twitch muscle lost glucose‑transport proteins and showed worse insulin resistance. The study suggests that boosting UPRmt or MOTS‑c in muscle might help guard against diet‑induced insulin resistance.

Utility 3
pubmed Jul 3, 2025

The impact of mitokine MOTS-c administration on the soleus muscle of rats subjected to a 7-day hindlimb suspension.

Sidorenko. Daria A DA; Lvova. Irina D ID; Tyganov. Sergey A SA; Shenkman. Boris S BS; Sharlo. Kristi...

A study in rats showed that daily injections of the tiny mitochondrial peptide MOTS‑c helped keep the slow‑twitch leg muscle from getting weaker, shrinking, or turning into fast‑twitch muscle during a week of forced inactivity. The peptide kept important muscle‑building signals active, reduced muscle‑breakdown signals, and preserved markers of mitochondrial health, which together reduced fatigue and muscle loss.

Utility 3
pubmed Nov 21, 2025

MOTS‑c protects against placental injury via Nrf2 activation in hypoxia‑induced intrauterine growth restriction mice.

Chen. Dan D; Zhao. Hui-Min HM; Sun. Xiao-Lin XL; Xing. Zhi-Xuan ZX; Li. Sheng-Peng SP; Li. Shuai-Cha...

In a mouse study, giving the tiny peptide MOTS‑c helped protect the placenta from low‑oxygen damage and let babies grow bigger by boosting blood‑vessel growth and cutting oxidative stress, but only when the Nrf2 antioxidant pathway was working. This suggests MOTS‑c can turn on Nrf2, a key defender against oxidative damage, though the work was done in pregnant mice, not people.

Utility 3
pubmed Nov 28, 2024

MOTS-c regulates the ROS/TXNIP/NLRP3 pathway to alleviate diabetic cardiomyopathy.

Fu. Yu Y; Tang. Mi M; Duan. Yimei Y; Pan. Yanrong Y; Liang. Min M; Yuan. Jinghan J; Wang. Manda M; L...

A study in diabetic rats found that giving the mitochondrial peptide MOTS‑c for eight weeks lowered heart inflammation and damage. It did this by cutting down harmful reactive oxygen species and blocking a key inflammation pathway (ROS/TXNIP/NLRP3). The results suggest MOTS‑c could protect the heart in diabetes, but the work was done in animals and used injections, not oral dosing.

Utility 3
pubmed May 17, 2019

Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation.

Lu. Huanyu H; Tang. Shan S; Xue. Chong C; Liu. Ying Y; Wang. Jiye J; Zhang. Wenbin W; Luo. Wenjing W...

The study shows that giving the mitochondrial peptide MOTS‑c helps mice handle cold better by turning more of their fat into heat‑producing brown fat and boosting the activity of existing brown fat. This effect seems to work through a cell‑signaling pathway called ERK. While the peptide lowered the drop in its own blood levels caused by cold, the research is still in animals and doesn’t give dosing details for people.

Utility 3
pubmed Jul 27, 2021

Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.

Kong. Byung Soo BS; Min. Se Hee SH; Lee. Changhan C; Cho. Young Min YM

A tiny protein made by mitochondria called MOTS‑c can protect the insulin‑producing cells in the pancreas from being attacked by the immune system in a mouse model of type‑1 diabetes, and it also calms down over‑active immune cells taken from people with the disease. This suggests it might one day be used to help prevent or treat autoimmune diabetes, but it’s still early research and not yet a ready‑to‑use supplement.

Utility 3
pubmed Nov 13, 2023

The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.

Tang. Mi M; Su. Quansheng Q; Duan. Yimei Y; Fu. Yu Y; Liang. Min M; Pan. Yanrong Y; Yuan. Jinghan J;...

In diabetic rats, giving the tiny protein MOTS‑c (0.5 mg per kg body weight each day) helped protect the heart, reduced damage, and improved its function. The benefits were similar to those seen with regular treadmill exercise and were even stronger when MOTS‑c was combined with exercise. The peptide boosted the heart’s natural antioxidant systems (SOD, CAT, Nrf2, p‑AMPK) and lowered harmful oxidative markers.

Utility 3
pubmed Sep 3, 2020

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.

Guo. Qi Q; Chang. Bo B; Yu. Qiong-Li QL; Xu. Si-Tong ST; Yi. Xue-Jie XJ; Cao. Shi-Cheng SC

In mice, giving adiponectin or the mitochondrial peptide MOTS‑c, or doing exercise, raises MOTS‑c levels in muscle and blood, which improves how the body handles sugar. The effect works through a chain of proteins called APPL1, SIRT1 and PGC‑1α. This suggests that boosting adiponectin or MOTS‑c could be a way to fight insulin resistance, but the work is still in animals, not people.

Utility 3
pubmed Aug 25, 2025

Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.

Kong. Byung Soo BS; Lee. Hyunsuk H; L'Yi. Sehi S; Hong. Serin S; Cho. Young Min YM

A tiny protein made by mitochondria called MOTS‑c drops as we age and in diabetic mice. Giving extra MOTS‑c to old mouse pancreas cells or to diabetic mice reduced signs of cell aging and helped lower blood sugar. In people with type‑2 diabetes, blood levels of MOTS‑c are also lower, hinting it might play a role in the disease.

Utility 3
pubmed Dec 18, 2024

Endurance training enhances skeletal muscle mitochondrial respiration by promoting MOTS-c secretion.

Feng. Yiwei Y; Rao. Zhijian Z; Tian. Xu X; Hu. Yi Y; Yue. Liantian L; Meng. Yifan Y; Zhong. Qiuling...

The study shows that regular endurance exercise, like marathon training, raises the level of a naturally occurring peptide called MOTS‑c in the blood. Higher MOTS‑c is linked to better aerobic performance and healthier muscle mitochondria, likely through the AMPK/PGC‑1α pathway. This suggests that MOTS‑c could be a useful biomarker for training progress and metabolic health.

Utility 3
pubmed 2025

MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate Cardiopulmonary Bypass-induced Lung Injury.

Shen. Zihao Z; Lu. Peng P; Jin. Wanjun W; Wen. Ziang Z; Qi. Yuanpu Y; Li. Xiangyu X; Chu. Mingyu M;...

MOTS‑c, a tiny protein made by mitochondria, helped protect lung cells from damage caused by heart‑lung machine use during surgery. It did this by turning on a sugar‑burning pathway (AMPK‑HIF‑1α‑PFKFB3) that kept cells energized and stopped a type of cell death called ferroptosis. Patients who got lung injury had lower blood levels of MOTS‑c, and giving the peptide before injury reduced inflammation and oxidative stress in lab models.

Utility 3
pubmed Apr 6, 2019

Earlier changes in mice after D-galactose treatment were improved by mitochondria derived small peptide MOTS-c.

Li. Qingyang Q; Lu. Huanyu H; Hu. Guangyu G; Ye. Zichen Z; Zhai. Dongsheng D; Yan. Zhao Z; Wang. Li...

In mice made to age faster with D-galactose, giving the mitochondrial peptide MOTS‑c helped clear excess fat in the liver, belly fat and skin, improved the tiny structures inside mitochondria, and reduced signs of aging in the gut, though it only slightly changed weight or blood sugar.

Utility 3
pubmed Feb 8, 2021

MOTS-c reduces myostatin and muscle atrophy signaling.

Kumagai. Hiroshi H; Coelho. Ana Raquel AR; Wan. Junxiang J; Mehta. Hemal H HH; Yen. Kelvin K; Huang....

MOTS‑c, a tiny protein made by mitochondria, can lower the muscle‑wasting hormone myostatin and protect muscle cells from shrinking, at least in lab dishes and obese mice. It does this by turning on a chain of signals (CK2 → PTEN ↓ → mTORC2 ↑ → AKT ↑ → FOXO1 ↓) that keep muscle‑breaking genes quiet.

Utility 3
pubmed Mar 17, 2022

MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats.

Li. Shunchang S; Wang. Manda M; Ma. Jiacheng J; Pang. Xiaoli X; Yuan. Jinghan J; Pan. Yanrong Y; Fu....

In diabetic rats, giving the mitochondrial peptide MOTS‑c or having the animals run on a treadmill both helped the heart stay healthier. The peptide acted like exercise, lowering inflammation, cell death, and improving blood‑vessel growth, and it did this by turning on a signaling pathway (NRG1‑ErbB4) that’s also activated by real exercise.

Utility 3
pubmed Dec 15, 2022

Orally administered MOTS-c analogue ameliorates dextran sulfate sodium-induced colitis by inhibiting inflammation and apoptosis.

Jiang. JinHong J; Chang. Xin X; Nie. YaoYan Y; Xu. Lingfei L; Yang. Long L; Peng. YaLi Y; Chang. Min...

In mouse experiments, giving the mitochondrial peptide MOTS‑c by injection helped protect the gut from inflammation caused by a chemical that mimics ulcerative colitis. The same peptide taken by mouth didn’t work, but when scientists attached a cell‑penetrating tag (making a new version called MP) it survived the gut and, when taken orally, also reduced the disease signs. The benefits included less weight loss, longer colon, lower inflammatory chemicals, and less cell death in the colon lining.

Utility 3
pubmed Oct 9, 2022

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.

Mohtashami. Zahra Z; Singh. Mithalesh K MK; Salimiaghdam. Nasim N; Ozgul. Mustafa M; Kenney. M Crist...

MOTS‑c is a tiny protein made by mitochondria that drops as we get older. When we’re stressed, it moves into the cell nucleus and helps turn on genes that protect metabolism and muscle health. Studies in animals and early human work suggest it could improve diabetes, heart health, bone loss, post‑menopausal weight gain, and even memory, making it a promising anti‑aging molecule.

Utility 3
pubmed Jul 12, 2021

Mitofusion is required for MOTS-c induced GLUT4 translocation.

Bhullar. Khushwant S KS; Shang. Nan N; Kerek. Evan E; Wu. Kaiyu K; Wu. Jianping J

MOTS‑c, a tiny peptide from mitochondria, can help cells pull more sugar into them by moving the GLUT4 transporter to the cell surface, but it only works if the cell’s mitochondria are fusing together properly. The study shows that MOTS‑c boosts proteins that drive mitochondrial fusion (OPA1 and MFN2) and that blocking these proteins stops the sugar‑uptake effect.

Utility 3
pubmed Oct 30, 2021

The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance.

Kumagai. Hiroshi H; Natsume. Toshiharu T; Kim. Su-Jeong SJ; Tobina. Takuro T; Miyamoto-Mikami. Eri E...

A common East Asian genetic variant (K14Q) that weakens the MOTS‑c peptide is linked to more fast‑twitch muscle fibers and better sprint/power performance, while higher MOTS‑c activity may favor slower, endurance‑type fibers. In mice, blocking MOTS‑c also boosted fast‑fiber proteins, supporting the human data.

Utility 3
pubmed Jan 5, 2024

Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection.

Lin. Caorui C; Luo. Linjie L; Xun. Zhen Z; Zhu. Chenggong C; Huang. Ying Y; Ye. Yuchen Y; Zhang. Jia...

Researchers found that the tiny mitochondrial peptide MOTS‑c is low in people with hepatitis B and that giving it to infected cells and mice cuts the virus by about half while improving liver health. It also boosts the cell's own antiviral signaling and helps make new, healthier mitochondria by working through a protein called MYH9 and the cell’s actin skeleton.