Journal Article Ppublish
PubMed: 40545685 DOI: 10.1002/pro.70207
Ancestral sequence reconstruction of the Mic60 Mitofilin domain reveals residues supporting respiration in yeast.
Protein Sci 34(7):e70207
Authors: Friederike M C Benning, Tristan A Bell, Tran H Nguyen, Della Syau, Louise B Connell, Yi-Ting Liao, Matthew P Keating, Margaret Coughlin, Anja E H Nordstrom, Maria Ericsson, Corrie J B daCosta, Luke H Chao
Affiliations
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
- Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Biology, Boston University, Boston, Massachusetts, USA.
- Electron Microscopy Core Facility, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
In eukaryotes, cellular respiration takes place in the cristae of mitochondria. The mitochondrial inner membrane protein Mic60, a core component of the mitochondrial contact site and cristae organizing system, is crucial for the organization and stabilization of crista junctions and its associated functions. While the C-terminal Mitofilin domain of Mic60 is necessary for cellular respiration, the sequence determinants for this function have remained unclear. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors, we identified four residues sufficient to explain the respiratory difference between yeast- and animal-derived Mitofilin ancestors. Our results provide a foundation for investigating the conservation of Mic60-mediated cristae junction interactions.
MeSH
Yeasts, Cell Respiration, Respiration, Mitochondria