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Research library, mechanism

Mitochondria-linked peptides: MOTS-c and SS-31

MOTS-c is a 16-residue peptide encoded in mitochondrial DNA. SS-31 is a synthetic tetrapeptide designed to target the inner mitochondrial membrane. Both are studied in mitochondrial biology, from different starting points: one is a natural signalling peptide, the other a designed molecule.

Written by the Peptency editorial teamLast reviewed 5 studies checked in PubMed on 5 October 2026

Research-use information. This page summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

What is MOTS-c?

MOTS-c was identified from a short open reading frame in the mitochondrial 12S rRNA gene. A later paper reported that it translocates to the nucleus in response to metabolic stress and regulates nuclear gene expression.[2],[1]

What is SS-31?

SS-31 was designed as a cell-permeable peptide that targets the inner mitochondrial membrane. Mechanism papers report that it interacts with cardiolipin and affects the cytochrome c and cardiolipin complex, electron transport and ATP synthesis. A review covers the development of inner-membrane-targeted peptides.[4],[3],[5]

Which compounds in the catalog belong to this group?

Mitochondria-encoded 16-residue peptideMOTS-c

C101H152N28O22S2, 2174.6 g/mol

Mitochondria-targeted tetrapeptideSS-31

C32H49N9O5, 639.8 g/mol

Research materials: MOTS-c, SS-31.

Which studies are cited on this page?

  1. [1] 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;28:516-524.e7.

    Showed that MOTS-c translocates to the nucleus under metabolic stress and regulates nuclear gene expression.

    In vitro and animal studyPMID 29983246DOI 10.1016/j.cmet.2018.06.008

  2. [2] Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21:443-54.

    Identified the MOTS-c open reading frame in mitochondrial DNA and reported its metabolic effects in cells and mice.

    In vitro and animal studyPMID 25738459DOI 10.1016/j.cmet.2015.02.009

  3. [3] Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. 2014;171:2017-28.

    Studied SS-31 binding to cardiolipin and its effect on the cytochrome c and cardiolipin complex, electron transport and ATP synthesis.

    Animal studyPMID 24134698DOI 10.1111/bph.12468

  4. [4] Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, et al.. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24:1250-61.

    Studied SS-31 interaction with cardiolipin and ATP recovery in ischaemic mitochondria in a kidney model.

    Animal studyPMID 23813215DOI 10.1681/ASN.2012121216

  5. [5] Szeto HH, Schiller PW. Novel therapies targeting inner mitochondrial membrane: from discovery to clinical development. Pharm Res. 2011;28:2669-79.

    Review of the discovery and development of peptides targeting the inner mitochondrial membrane, including SS-31.

    ReviewPMID 21638136DOI 10.1007/s11095-011-0476-8

Data dates: citations read from PubMed 2026-10-05.