Also known as: 1627580-64-6, UNII-A5CV6JFB78, MOTS-c (human) (trifluoroacetate salt), A5CV6JFB78, H-MRWQEMGYIFYPRKLR-OH, orb2279120, orb3032863, SCHEMBL29545955
MOTS-c (1627580-64-6, UNII-A5CV6JFB78, MOTS-c (human) (trifluoroacetate salt)) is classified under mitochondrial-derived & protective, sold for research use only and not approved for human consumption.
Aggregated from the cited literature below. We summarize sources — we don't author claims.
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a mitochondrial-derived peptide that consists of 16 amino acids and is encoded by the mitochondrial 12S rRNA region. Research has reported that MOTS-c can be transferred to the nucleus during metabolic stress and regulate nuclear gene expression, and that it is associated with regulation of metabolic homeostasis and insulin sensitivity, with reported links to age- and metabolism-related diseases. It has also been studied in cancer biology, where reports describe reduced levels in ovarian cancer tissues/serum and an inhibitory effect on ovarian cancer cell progression via interactions involving LARS1 ubiquitination and USP7-mediated deubiquitination.
Mechanism (as reported)
A study reported that MOTS-c translocates to the nucleus after metabolic stress and regulates nuclear gene expression in an AMPK-dependent manner, including genes with antioxidant response elements (ARE) and interactions with stress-responsive transcription factors such as NFE2L2/NRF2. (PMID 29983246) Another study reported that MOTS-c actions inhibit the folate cycle and tethered de novo purine biosynthesis, leading to AMPK activation; its primary target organ was described as skeletal muscle. (PMID 25738459) In ovarian cancer, a study reported that MOTS-c interacts with LARS1 and promotes LARS1 ubiquitination and proteasomal degradation; it also described attenuation of USP7-mediated LARS1 deubiquitination via competitive binding to LARS1. (PMID 39321430)
Key findings (each cites a source)
MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded by the mitochondrial 12S rRNA region/type-C sORF. [PMID 36761202, 25738459, 36233287, 29983246]
A study reported that MOTS-c translocates to the nucleus following metabolic stress and regulates nuclear gene expression via an AMPK-dependent manner, including regulation of genes containing antioxidant response elements (ARE) and interaction with NFE2L2/NRF2. [PMID 29983246]
A study reported that MOTS-c promotes metabolic homeostasis and regulates insulin sensitivity, with skeletal muscle described as a primary target organ. [PMID 25738459]
A study reported that MOTS-c cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, leading to AMPK activation. [PMID 25738459]
A study reported that MOTS-c levels decrease with age, with plasma also containing the peptide but showing reduced levels over time. [PMID 36761202, 36233287]
A study reported that MOTS-c can improve glucose metabolism/insulin resistance phenotypes in skeletal muscle contexts and was discussed as beneficial for diseases such as diabetes, obesity, and aging in a synthesis of findings. [PMID 36761202, 25738459, 36233287, 36824008]
A study reported reduced MOTS-c levels in serum and tumor tissues from ovarian cancer patients, associated with poor prognosis. [PMID 39321430]
A study reported that exogenous MOTS-c inhibited proliferation, migration, and invasion of ovarian cancer cells and induced cell cycle arrest and apoptosis. [PMID 39321430]
A study reported that in ovarian cancer, MOTS-c interacts with LARS1 to promote its ubiquitination and proteasomal degradation, and attenuates USP7-mediated LARS1 deubiquitination by competing with USP7 for LARS1 binding. [PMID 39321430]
A study reported that MOTS-c was evaluated in a gestational diabetes mellitus (GDM) mouse model and that it alleviated hyperglycemia and improved insulin sensitivity/glucose tolerance while also addressing offspring reproductive outcomes described in that study. [PMID 36824008]
A review summarized that MOTS-c is implicated in age-related diseases including diabetes, cardiovascular disease, osteoporosis/postmenopausal obesity, and Alzheimer, and described stress-induced nuclear regulatory roles. [PMID 36233287, 36824008, 36761202]
A review summarized that MOTS-c is encoded by the mitochondrial 12S rRNA short open reading frame, translocates to the nucleus under stress, regulates stress adaptation-related genes with ARE, and is linked in summaries to the Folate-AICAR-AMPK pathway and connections to insulin resistance, inflammatory response, exercise, aging, and aging-related pathologies. [PMID 36670507]
Independent HPLC purity tests (430)
Real third-party HPLC results aggregated from Peptigrity, each attributed to the lab that ran it — average purity 99.4% across 430 tests. Not our verdict.
Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J · Cell metabolism · 2015 · PMID 25738459
FAQ
What is MOTS-c?
MOTS-c (1627580-64-6, UNII-A5CV6JFB78, MOTS-c (human) (trifluoroacetate salt)) is classified under mitochondrial-derived & protective, sold for research use only and not approved for human consumption. Research goals associated with it include metabolic & weight, longevity & cellular aging.
Is MOTS-c FDA-approved?
No. MOTS-c is sold for research use only and is not approved for human consumption.
What does the research on MOTS-c say?
peptideone aggregates 8 references from PubMed for MOTS-c. The summary on this page digests them with citations; we summarize sources and make no efficacy claims.