MOTS-C

What is MOTS-c?

MOTS-c stands for “mitochondrial open reading frame of the 12S rRNA-c”. It was described in 2015 by Changhan Lee, Pinchas Cohen and colleagues at the University of Southern California, who found a 51-base-pair open reading frame in mitochondrial DNA that codes for a 16-amino-acid peptide. That makes it one of the “mitochondrial-derived peptides”, alongside humanin: small peptides encoded in the mitochondrial genome itself. It circulates in human and rodent blood.

In the discovery work its main target organ appeared to be skeletal muscle. In cells it inhibited the folate cycle and the linked purine synthesis, which in turn activated AMPK, the cell’s energy sensor. A 2018 study found that under metabolic stress MOTS-c moves into the nucleus and regulates nuclear genes, and a 2024 study identified protein kinase CK2 as a direct binding partner. No cell-surface receptor has been identified. It is often grouped with SS-31, a very different, synthetic peptide that binds cardiolipin in the mitochondrial membrane.

MOTS-c identity

Sources: PubChem, UniProt, the FDA substance registry (GSRS) and FDA’s July 2026 briefing document on MOTS-c. GSRS lists 2170 as a calculated weight; PubChem, UniProt and FDA give 2174.6–2175.

Certificates for the current lots

Each size is filled from its own lot and analysed separately by ILS Laboratories in San Diego, which states ISO/IEC 17025 accreditation for activities within its published scope. Both certificates are full QC panels: HPLC purity, net peptide content and identity, plus endotoxin, sterility, heavy metals by ICP-MS and a fentanyl screen:

MOTS-c price

Price per vial and per milligram, read live from the store:

Published research on MOTS-c

• Discovery (cells and mice, 2015). The short ORF in the 12S rRNA, the 16-residue peptide it encodes, folate-cycle inhibition and AMPK activation, studied in cultured cells and in aged and high-fat-fed mice. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C, et al. Cell Metabolism, 2015.
• Nuclear translocation (cells, 2018). Under glucose restriction and other metabolic stress, MOTS-c moved into the nucleus in an AMPK-dependent way and regulated nuclear genes, including antioxidant-response genes, interacting with NRF2. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Kim KH, et al. Cell Metabolism, 2018.
• Exercise and muscle (mice and humans, 2021). Physical performance was measured in young, middle-aged and old mice given MOTS-c; in people, exercise raised endogenous MOTS-c in muscle and blood. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC, et al. Nature Communications, 2021.
• Plasma metabolites (mice, 2019). Untargeted metabolomics in diet-induced obese mice found changes in sphingolipid, monoacylglycerol and dicarboxylate metabolism after MOTS-c. Kim SJ, et al. Physiological Reports, 2019.
• CK2 as a direct target (2024). MOTS-c bound and activated protein kinase CK2 in cell-free assays, and its effects on mouse muscle were blunted when CK2 was suppressed. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. Kumagai H, et al. iScience, 2024.
• A natural variant (human cohorts, 2021). An Asian-specific mitochondrial DNA variant, m.1382A>C, changes lysine 14 to glutamine (K14Q-MOTS-c); in 27,527 people its association with type 2 diabetes was studied by sex and activity level. Zempo H, et al. Aging, 2021.
• Endogenous levels in people (2018, 2021). Plasma MOTS-c was similar in lean and obese adults; after a single endurance bout it showed only a non-significant upward trend. Cataldo LR, et al., 2018; von Walden F, et al., 2021.

No clinical study of administered MOTS-c had been published by October 2026. CohBar’s analogue CB4211 completed a phase 1a/1b study (NCT03998514), and a phase 2a study of MOTS-c itself was registered in China in 2026 (NCT07505745).

Regulatory status

MOTS-c is not an approved drug anywhere. FDA placed it in its 503A compounding category 2 (substances that may present significant safety risks) on 29 September 2023; the page now lists it among substances nominated and then withdrawn. At its July 2026 Pharmacy Compounding Advisory Committee meeting FDA proposed not adding MOTS-c to the compounding bulks list, noting no human exposure data. WADA’s 2026 Prohibited List names MOTS-c among AMPK activators, prohibited at all times. FDA compounding safety-risk list; FDA briefing document on MOTS-c, July 2026; WADA Prohibited List. Clean Peptide’s MOTS-c is a laboratory reference material only, not for human or veterinary use.

Related research

• SS-31 (elamipretide), the cardiolipin-binding mitochondrial peptide.
• Epithalon and NAD+ in cellular-ageing research.
• SLU-PP-332 and 5-Amino-1MQ, small-molecule metabolic research compounds.
• All longevity and mitochondrial peptides.