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Ancient mitochondrial DNA yields antimicrobial peptides

Researchers searched 2,025 ancient human mitogenomes for peptide‑encoding sequences, translated the DNA into possible amino‑acid chains, modeled where cellular enzymes could cut them, and used a machine‑learning model to select 65 candidates from 741,575 fragments. They then synthesized 38 peptides and tested their ability to inhibit growth of 16 bacterial strains.

One peptide, mitochondrin-32, inhibited growth of ten strains. Swapping a few amino acids changed activity, indicating that a precise configuration of hydrophobic and positively charged residues is required for the antibacterial effect.

Fluorescent dyes that report membrane permeability and inner‑membrane potential showed that some peptides gave a strong signal, others a weak one, even though both suppressed bacterial growth. The authors suggest that mitochondrially derived peptides (mitocrins) act through several pathways against bacteria.

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bioRxiv
Ancient human mitochondrial genomes encode antimicrobial peptides
Mitochondria are bacteria-derived organelles that coordinate major innate immune pathways, but whether mitochondrial genomes themselves encode direct antimicrobial functions is underexplored. Here, we test the hypothesis that ancient human mitochondrial DNA…
August 26, 2026 4