MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide
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…
MOTS-c, a mitochondrial-encoded host defense peptide, has been identified in the human mitochondrial genome. This peptide, derived from the primordial proto-mitochondrial bacteria, possesses antibacterial and immunomodulatory properties. MOTS-c effectively neutralizes Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) by targeting their membranes.
In a mouse model of acute peritonitis, MOTS-c completely eliminated MRSA infectivity. Human monocytes, when exposed to interferon gamma (IFNγ), lipopolysaccharides (LPS), or differentiation signals, express endogenous MOTS-c. Exogenous MOTS-c, applied during primary mouse monocyte differentiation, transforms the cells into macrophages with unique transcriptomic profiles related to antigen presentation and IFN signaling.
These macrophages exhibit improved bacterial clearance and altered metabolism. The research indicates that MOTS-c is a first-in-class mitochondrial-encoded host defense peptide, suggesting that our immune system is encoded not only by the nuclear genome but also by the co-evolved mitochondrial genome.
Written by urgent.news from eLife's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
