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

Experimental study involving in vitro bacterial and cell assays, and in vivo mouse infection models

“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.”

Bacteria (E. coli, MRSA), human monocytes/macrophages (THP-1, primary), and C57BL/6J mice

“MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains.”

Varies by experiment; e.g., n=5-6 mice per group for in vivo survival, n=6 for most in vitro assays, N=5 animals per group for single-cell RNA-seq

“MRSA preparations were then immediately injected IP into 6-month-old female C57BL/6J mice (n=5–6).”

In vivo monitoring for 72 hours; in vitro differentiation and stimulation assays ranging from 2 hours to 7 days

“Survival and (B) weight were monitored for 72 hr.”

MOTS-c is a mitochondrial-encoded host defense peptide with direct antibacterial activity against E. coli and MRSA

“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 treatment neutralized MRSA infectivity and enhanced survival in a mouse model of acute peritonitis

“In a mouse model of acute peritonitis, MOTS-c fully neutralized MRSA infectivity.”

MOTS-c reprograms monocyte differentiation into macrophages with distinct transcriptomic signatures related to antigen presentation and interferon signaling

“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.”

The study notes that limited sample numbers require future work to elucidate interactions of MOTS-c treatment with age and sex in BMDM transcriptional programming

“With limited sample number, future work will be needed to elucidate interactions of MOTS-c treatment with age and sex in the context of BMDM transcriptional programming.”