Saccharomyces cerevisiae Dmo2p is required for the stability and maturation of newly translated Cox2p

Author(s)

Soares, Maria Antonia Kfouri Martins ; Franco, Leticia Veloso Ribeiro ; Chagas, Jhulia Almeida Clarck ; Gomes, Fernando ; Barros, Mario H.

• Document type: Journal article
• Source: FEBS Journal; v. N/A, p. 19-pg., 2025-02-11.

Abstract

Based on available platforms detailing the Saccharomyces cerevisiae mitochondrial proteome and other high-throughput studies, we identified the yeast gene DMO2 as having a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homologue to human distal membrane-arm assembly complex protein 1 (DMAC1); both proteins have two conserved cysteines in a Cx(2)C motif. Here, we localised Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The respiratory deficiency of dmo2 mutants at 37 degrees C led to a reduction in cytochrome c oxidase (COX) activity (COX) and in the formation of cytochrome bc(1) complex-COX supercomplexes; dmo2 also has a rapid turnover of Cox2p, the second subunit of the COX complex that harbours the binuclear Cu-A centre. Moreover, Dmo2p co-immunoprecipitates with Cox2p and components required for maturation of the Cu-A centre, such as Sco1p and Sco2p. Finally, DMO2 overexpression can suppress cox23 respiratory deficiency, a mutant that has impaired mitochondrial copper homeostasis. Mass spectrometry data unveiled the interaction of Dmo2p with different large molecular complexes, including bc(1)-COX supercomplexes, the TIM23 machinery and the ADP/ATP nucleotide translocator. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p. (AU)

• FAPESP's process: 16/00696-3 - Proteomic as a tool to understand HDL function and composition
• Grantee: Graziella Eliza Ronsein
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/05812-7 - Regulation events for mitoribossome biogenesis and respiratory complexes assembly
• Grantee: Mario Henrique de Barros
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/02799-2 - ATCO1, a mitochondrial master regulator of ATP synthase and cytochrome oxidase biogenesis?
• Grantee: LETICIA VELOSO RIBEIRO FRANCO
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 22/02744-6 - Identification of new regulation factors of mitochondrial translation in Saccharomyces cerevisiae
• Grantee: Maria Antônia Kfouri Martins Soares
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/12663-1 - Singlet molecular oxygen and peroxides in chemical biology
• Grantee: Paolo Di Mascio
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/08559-6 - Study of the mitochondrial cytochrome c oxidase assembly regulation: from gene expression to supercomplex formation
• Grantee: Jhulia Almeida Clarck Chagas
• Support Opportunities: Scholarships in Brazil - Doctorate