2025/06/22 by Friederike M. C. Benning, Tristan A. Bell, Tran H. Nguyen +9 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Genetics, Aging, and Longevity in Model Organisms #Studies on Chitinases and Chitosanases #Cardiomyopathy and Myosin Studies
paper · pdf · doi:10.1002/pro.70207
openalex publication_date 2025/06/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/24
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.