Comparative analysis of mitochondrial proteomes across the tree of life
- 1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- 2Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA
- 3Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: [email protected]
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.
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BibTeX
@article{chen2026comparative,
title = {{Comparative analysis of mitochondrial proteomes across the tree of life}},
author = {Michael Z. Chen and Jonathan A. Stefely and Eric G. Bardon and Ruslan Aphasizhev and Inna Aphasizheva and Cora N. Betsinger and Steven A. Carr and Luke H. Chao and Felicia G. Deng and Manoj T. Duraisingh and Michelle Y. Fry and Manish Goyal and Tiana M. Issa and Minsoo Kim and Cameron Genxuan Lian and Yi-Ting Liao and Bridget E Luce and Syed Yusuf Mian and Khanh Nguyen and Aditya S. Paul and Keith D. Rivera and John Crawford Samuelson and Md Solayman and Namrata D. Udeshi and Andres F. Vacas and Sarah E. Calvo and Vamsi Krishna Mootha},
journal = {Cell},
year = {2026},
month = oct,
doi = {10.1016/j.cell.2026.08.029},
url = {https://doi.org/10.1016/j.cell.2026.08.029},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative analysis of mitochondrial proteomes across the tree of life
AU - Michael Z. Chen
AU - Jonathan A. Stefely
AU - Eric G. Bardon
AU - Ruslan Aphasizhev
AU - Inna Aphasizheva
AU - Cora N. Betsinger
AU - Steven A. Carr
AU - Luke H. Chao
AU - Felicia G. Deng
AU - Manoj T. Duraisingh
AU - Michelle Y. Fry
AU - Manish Goyal
AU - Tiana M. Issa
AU - Minsoo Kim
AU - Cameron Genxuan Lian
AU - Yi-Ting Liao
AU - Bridget E Luce
AU - Syed Yusuf Mian
AU - Khanh Nguyen
AU - Aditya S. Paul
AU - Keith D. Rivera
AU - John Crawford Samuelson
AU - Md Solayman
AU - Namrata D. Udeshi
AU - Andres F. Vacas
AU - Sarah E. Calvo
AU - Vamsi Krishna Mootha
PY - 2026
DA - 2026/10/01
JO - Cell
DO - 10.1016/j.cell.2026.08.029
UR - https://doi.org/10.1016/j.cell.2026.08.029
AB - 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.
SN - 0092-8674
SN - 1097-4172
ER -