What this means
Researchers found a small peptide made by mitochondrial DNA that can kill some bacteria. It was tested mostly in mice and in cells grown in a dish, so it does not show what happens in people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Mice, human immune cells and mouse immune cells in a lab, plus bacteria grown in a dish
- Kind of research
- A study
The science
- Original title
- MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide.
- Authors
- Rice MC, Imun M, Jung SW et al.
- Journal
- eLife
- Published
- Aug 18, 2026
- Study type
- Study · in humans
- PMID
- 42611943 ↗
Abstract
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.
Rice MC, Imun M, Jung SW et al. MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide. eLife. 2026. doi:10.7554/eLife.87615. PMID: 42611943. https://pubmed.ncbi.nlm.nih.gov/42611943/
Related research
AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition.
Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction.
Emerging regulators of human physiology and disease; sORF-encoded microproteins.
The human genome contains hundreds of thousands of short open reading frames (sORFs), yet their translational products, hereafter referred to as sORF-encoded microproteins (also historically termed micropeptides), have…
Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.
Cardiovascular disease is strongly influenced by mitochondrial dysfunction, yet how mitochondrial stress is communicated beyond the affected cell to coordinate systemic responses remains incompletely understood.
Blood marker MOTS-c linked to fitness in young men
Researchers compared 30 young men who were athletes, active, or inactive. Men with higher fitness tended to have higher levels of this blood marker.
Mitochondrial-derived peptides in female reproduction: Emerging regulators of oocyte competence and novel therapeutic opportunities for infertility.
Female infertility affects approximately 17.5% of adults worldwide. Mitochondria are central to oocyte developmental competence, and a novel class of mitochondrial genome-encoded peptides, mitochondrial-derived…
Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review.
BACKGROUND: Type 2 diabetes mellitus and metabolic diseases are increasing worldwide and are closely linked to mitochondrial dysfunction.