Characterization of Dmo2 in Cox2p biosynthesis of Saccharomyces cerevisiae mitochondria

• Grant number: 23/12800-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: April 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Mario Henrique de Barros
• Grantee: Maria Antônia Kfouri Martins Soares
• Supervisor: Martin Ott
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Gothenburg, Sweden
• Associated to the scholarship: 22/02744-6 - Identification of new regulation factors of mitochondrial translation in Saccharomyces cerevisiae, BP.DD

Abstract

In Saccharomyces cerevisiae, the mitochondrial DNA (mtDNA) is responsible for coding seven proteins that are subunits of the OXPHOS complexes. Cox2p, encoded by the mtDNA, is one of the proteins comprising the catalytic core of cytochrome c oxidase, and it is associated with two atoms of copper (CuA center). Cox2p has two transmembrane domains that count on several proteins to be correctly inserted in the mitochondrial inner membrane, as well as the CuA site that receives two atoms of copper in a process mediated mainly by Cox17p, Sco1p, Sco2p as the copper deliverers. After in silico research of promisor candidates to be characterized, our group focused on Saccharomyces cerevisiae ORF YDL157c, or DMO2, a homolog of human DMAC1, which is involved in the human respirasome formation. Our laboratory recently described the uncharacterized protein Dmo2p as a moonlight protein that is involved in Cox2p stability. Dmo2p was shown to interact with Sco1p, Sco2p and Cox2p itself, and forms a complex with Sco1p with a molecular weight higher than 144kDa. In this project, we propose to better characterize Dmo2p role in Cox2p biosynthesis by identifying its interactors and proximal proteins with a biotinylation-based technique called BioID, and by solving the structure of the complex comprising Dmo2p and other proteins involved in Cox2p biosynthesis with cryogenic electron microscopy.