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Study · Animal study (in vivo) · mouse · 2026

8 results

MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide.

Rice MC, Imun M, Jung SW, Park CY, Kim JS, Lai RW, Barr CR, Son JM, Tor K, Kim E, Lu RJ, Cohen I, Benayoun BA, Lee C

eLife18 Aug 2026

PMID42611943 (opens in a new tab)PMCIDPMC13485304 (opens in a new tab)DOI10.7554/elife.87615 (opens in a new tab)PepBankPUB-42611943
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Summary

The mitochondrial DNA (mtDNA) can trigger immune responses and directly entrap pathogens, but it is not known to encode active immune factors. The immune system is traditionally thought to be exclusively nuclear-encoded. Here, we report the identification of a host defense peptide (HDP) encoded in the human mitochondrial genome that presumably derives from the primordial proto-mitochondrial bacteria. We demonstrate that MOTS-c (mitochondrial open reading frame from the 12 S rRNA type-c) is a mitochondrial-encoded amphipathic and cationic peptide with direct antibacterial and immunomodulatory functions, consistent with the peptide chemistry and functions of known HDPs. MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains. In a mouse model of acute peritonitis, MOTS-c fully neutralized MRSA infectivity. In human monocytes, interferon gamma (IFNγ), lipopolysaccharides (LPS), and differentiation signals each induced the expression of endogenous MOTS-c. Notably, exogenous MOTS-c, applied during primary mouse monocyte differentiation, reprogrammed the cells into macrophages with distinct transcriptomic signatures related to antigen presentation and IFN signaling. MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism. Our findings support MOTS-c as a first-in-class mitochondrial-encoded HDP and indicate that our immune system is not only encoded by the nuclear genome but also by the co-evolved mitochondrial genome.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In a mouse model of acute peritonitis, MOTS‑c fully neutralized MRSA infectivity.

    In plain wordsIn mice with peritonitis, MOTS‑c fully neutralized MRSA infection.

    Peptide
    MOTS-c
    Outcome
    DecreaseMRSA infectivity in acute peritonitis
    Study

    mousen: not reported in source

    Acute peritonitis model
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In a mouse model of acute peritonitis, MOTS-c fully neutralized MRSA infectivity.
  2. 02LabIn vitro (cells)Activity measurement

    In lab tests, MOTS‑c targeted Escherichia coli.

    In plain wordsIn lab tests, MOTS‑c acted against E. coli bacteria.

    Peptide
    MOTS-c
    Outcome
    DecreaseAntibacterial activity against E. coli
    Study

    n: not reported in source

    Escherichia coli
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains.
  3. 03LabIn vitro (cells)Activity measurement

    In lab tests, MOTS‑c targeted methicillin-resistant Staphylococcus aureus.

    In plain wordsIn lab tests, MOTS‑c acted against MRSA bacteria.

    Peptide
    MOTS-c
    Outcome
    DecreaseAntibacterial activity against MRSA
    Study

    n: not reported in source

    Methicillin-resistant Staphylococcus aureus (MRSA)
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains.
  4. 04LabIn vitro (cells)Mechanism

    In lab tests, MOTS‑c targeted E. coli and MRSA in part by acting on their membranes through its hydrophobic and cationic domains.

    In plain wordsIn lab tests, MOTS‑c attacked bacteria partly by acting on their membranes.

    Peptide
    MOTS-c
    Outcome
    Not applicableBacterial membrane targeting
    Study

    n: not reported in source

    Escherichia coli and MRSA
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains.
  5. 05LabIn vitro (cells)Mechanism

    Exogenous MOTS‑c applied during mouse monocyte differentiation reprogrammed cells into macrophages with distinct transcriptomic signatures related to antigen presentation and IFN signaling.

    In plain wordsIn mouse immune cells, MOTS‑c changed gene activity linked to antigen presentation and interferon signalling.

    Peptide
    MOTS-c
    Outcome
    Not applicableMacrophage transcriptome after MOTS-c during differentiation
    Study

    mousen: not reported in source

    Primary mouse monocytes
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Notably, exogenous MOTS-c, applied during primary mouse monocyte differentiation, reprogrammed the cells into macrophages with distinct transcriptomic signatures related to antigen presentation and IFN signaling.
  6. 06LabIn vitro (cells)Efficacy outcome

    MOTS‑c-programmed macrophages showed enhanced bacterial clearance.

    In plain wordsIn cells, macrophages treated with MOTS‑c cleared bacteria better.

    Peptide
    MOTS-c
    Outcome
    IncreaseBacterial clearance by macrophages
    Study

    mousen: not reported in source

    MOTS-c-programmed macrophages
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism.
  7. 07LabIn vitro (cells)Mechanism

    MOTS‑c-programmed macrophages showed shifted metabolism.

    In plain wordsIn cells, macrophages treated with MOTS‑c changed their metabolism.

    Peptide
    MOTS-c
    Outcome
    Direction not reportedMacrophage metabolism
    Study

    mousen: not reported in source

    MOTS-c-programmed macrophages
    Outcome group
    Mitochondrial function · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 08LabEndogenous levelIn vitro (cells)Mechanism

    In human monocytes, interferon gamma, lipopolysaccharides and differentiation signals each induced expression of the cells' own MOTS‑c.

    In plain wordsIn human immune cells, infection signals made the cells produce more of their own MOTS‑c.

    Peptide
    MOTS-c
    Outcome
    IncreaseEndogenous MOTS-c expression in monocytes
    Study

    humann: not reported in source

    Human monocytes
    Outcome group
    Immune response · Immune and inflammation

    Source sentences

    Summary
    In human monocytes, interferon gamma (IFNγ), lipopolysaccharides (LPS), and differentiation signals each induced the expression of endogenous MOTS-c.

    This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 02:56 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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