Overexpression of MRX9 impairs processing of RNAs encoding mitochondrial oxidative phosphorylation factors COB and COX1 in yeast

Author(s)

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

• Document type: Journal article
• Source: Journal of Biological Chemistry; v. 298, n. 8, p. 16-pg., 2022-07-21.

Abstract

Mitochondrial translation is a highly regulated process, and newly synthesized mitochondrial products must first associate with several nuclear-encoded auxiliary factors to form oxidative phosphorylation complexes. The output of mitochondrial products should therefore be in stoichiometric equilibrium with the nuclear-encoded products to prevent unnecessary energy expense or the accumulation of pro-oxidant assembly modules. In the mitochondrial DNA of Saccharomyces cerevisiae, COX1 encodes subunit 1 of the cytochrome c oxidase and COB the central core of the cytochrome bc1 electron transfer complex; however, factors regulating the expression of these mitochondrial products are not completely described. Here, we identified Mrx9p as a new factor that controls COX1 and COB expression. We isolated MRX9 in a screen for mitochondrial factors that cause poor accumulation of newly synthesized Cox1p and compromised transition to the respiratory metabolism. Northern analyses indicated lower levels of COX1 and COB mature mRNAs accompanied by an accumulation of unprocessed transcripts in the presence of excess Mrx9p. In a strain devoid of mitochondrial introns, MRX9 overexpression did not affect COX1 and COB translation or respiratory adaptation, implying Mrx9p regulates processing of COX1 and COB RNAs. In addition, we found Mrx9p was localized in the mitochondrial inner membrane, facing the matrix, as a portion of it cosedimented with mitoribosome subunits and its removal or overexpression altered Mss51p sedimentation. Finally, we showed accumulation of newly synthesized Cox1p in the absence of Mrx9p was diminished in cox14 null mutants. Taken together, these data indicate a regulatory role of Mrx9p in COX1 RNA processing. (AU)

• 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: 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: 19/23984-2 - Identification of MRX factors involved in mitochondrial translation
• Grantee: Maria Antônia Kfouri Martins Soares
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC