Mitochondrial Peptides

What defines a mitochondrial peptide?

The term covers two different groups. The first is mitochondrial-derived peptides: short peptides read from small open reading frames inside mitochondrial DNA. MOTS-c belongs here. It was described in 2015 as a 16-residue peptide encoded in the 12S rRNA gene, studied mainly in mouse skeletal muscle and cultured cells [R1]. Later work in cells reported that it can move to the nucleus under metabolic stress [R3].

The second group is mitochondria-targeted synthetic peptides. These are designed in the lab, not encoded in any genome. SS-31 is the best-known example. It alternates aromatic and basic residues and was reported to concentrate in the inner mitochondrial membrane [R4], where it binds the phospholipid cardiolipin [R2].

So the two compounds share a location, not a mechanism. For a side-by-side look, see MOTS-c vs SS-31.

Mitochondrial peptides at Sequora

Sources: MOTS-c identity from the FDA briefing document and FDA UNII record [R5][R6]; SS-31 identity from the FDA UNII record and FDA prescribing information [R7][R8]. SS-31 molecular weight is calculated from its formula.

Regulatory status

MOTS-c is not an approved drug. FDA states it is not a component of any FDA-approved drug and found no clinical studies of it in humans [R5]. It was removed from FDA's 503A "Category 2" list in April 2026 after its nomination was withdrawn [R9]. In July 2026 an FDA advisory committee voted 7–5–2 to recommend it for the 503A bulks list; the vote is non-binding and FDA rulemaking is still required [R10].

Elamipretide received FDA accelerated approval on September 19, 2025, as a drug product for one rare mitochondrial disease, Barth syndrome, in patients weighing at least 30 kg; continued approval depends on a confirmatory trial [R11]. Sequora's SS-31 is a research chemical, not that approved drug product.

Mitochondrial peptides FAQ

What are mitochondrial peptides?

They are short peptides linked to mitochondria. Some, like MOTS-c, are encoded in mitochondrial DNA [R1]. Others, like SS-31, are synthetic peptides designed to reach the inner mitochondrial membrane [R4].

Is SS-31 a mitochondrial-derived peptide?

No. SS-31 is a synthetic tetrapeptide containing a D-amino acid and a modified tyrosine. It is not encoded in any genome [R8].

Are MOTS-c and SS-31 FDA-approved?

MOTS-c is not approved for any use [R5]. Elamipretide has accelerated approval for Barth syndrome only [R11]. Research-labeled SS-31 is not an approved product.

How are these peptides stored?

Store the lyophilized powder at −20 °C, protected from light and moisture. Check the batch COA for lot-specific handling notes; our guide on how to read a peptide COA explains each field.

Are these peptides for human use?

No. These compounds are sold for in-vitro and laboratory research only. See research-use-only peptides explained.

References

1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009. PMID 25738459.
2. Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250–1261. doi:10.1681/ASN.2012121216. PMID 23813215.
3. Kim KH, Son JM, Benayoun BA, Lee C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018;28(3):516–524.e7. doi:10.1016/j.cmet.2018.06.008. PMID 29983246.
4. Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279(33):34682–34690. doi:10.1074/jbc.M402999200. PMID 15178689.
5. U.S. Food and Drug Administration. FDA briefing document: MOTS-c-related bulk drug substances (MOTS-c (free base) and MOTS-c acetate). Pharmacy Compounding Advisory Committee, July 23–24, 2026. fda.gov/media/193347/download
6. U.S. Food and Drug Administration. UNII A5CV6JFB78: Mitochondria-derived peptide MOTS-C. Global Substance Registration System. precision.fda.gov
7. U.S. Food and Drug Administration. UNII 87GWG91S09: Elamipretide. Global Substance Registration System. precision.fda.gov
8. U.S. Food and Drug Administration. Elamipretide prescribing information, NDA 215244 (2025). accessdata.fda.gov
9. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (content current as of April 22, 2026). fda.gov
10. McDermott Will & Schulte. Bulk list bound? PCAC backs majority of peptides in two-day public meeting. July 2026. mcdermottlaw.com
11. U.S. Food and Drug Administration. FDA grants accelerated approval to first treatment for Barth syndrome. Press announcement, September 19, 2025. fda.gov

For laboratory research use only. Not for human or veterinary use.