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Cell· 2026Q1

Comparative analysis of mitochondrial proteomes across the tree of life

Michael Z. Chen, Jonathan A. Stefely, Eric G. Bardon, Ruslan Aphasizhev et al.

Short summary

A comparative analysis of experimentally defined mitoproteomes across eight organisms identified 8,619 distinct mitochondrial proteins within 3,199 families, revealing 33 protein families conserved in eukaryotic pathogens but absent in humans, and reconstructing the complex, metabolically flexible mitoproteome of the last eukaryotic common ancestor (LECA).

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Key points

  • Identified 8,619 distinct mitochondrial proteins within 3,199 families across eight organisms.
  • Found 43% of identified mitochondrial proteins lack Pfam domains.
  • Discovered 33 protein families conserved in eukaryotic pathogens but absent in humans.
  • Reconstructed the last eukaryotic common ancestor (LECA) mitoproteome, showing capacity for aerobic and anaerobic metabolism.

AI-generated from the title and abstract; the full text is not read.

Abstract

Mitochondria arose from the endosymbiosis of a bacterium with an archaea-related host cell about 2 billion years ago. To understand their origins and evolution, we compared experimentally defined mitoproteomes from the MitoCarta Tree of Life project. Across eight organisms, we identified 8,619 distinct mitochondrial proteins within 3,199 families, of which 43% lack Pfam domains. We report 33 protein families conserved in eukaryotic pathogens yet absent in humans, representing promising candidate targets for protozoan infectious diseases. Leveraging our experimentally defined mitoproteomes, we retrained a classifier based on a protein language model to predict mitoproteomes of ∼200 eukaryotes. From this expanded set, we detail the evolutionary trajectories of mitochondria, ranging from clade-specific gene family expansions to extreme mitoproteome reductions seemingly en route to complete organelle loss. Finally, we reconstruct the last eukaryotic common ancestor (LECA) mitoproteome, revealing that LECA possessed a complex mitochondrion capable of both aerobic and anaerobic metabolism.

The authors' abstract, as published at the source. Cell, 2026 · DOI ↗

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Field: Molecular Biology

Molecular BiologyBiochemistry, Genetics and Molecular Biology