Regulation events for mitoribossome biogenesis and respiratory complexes assembly

• Grant number: 20/05812-7
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2020
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Mario Henrique de Barros
• Grantee: Mario Henrique de Barros
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Leticia Veloso Ribeiro Franco

Abstract

Mitochondrial mitoribosomes are responsible for the translation of mitochondrially encoded mRNAs. The mitoribosome was adapted along evolution to optimize the expression of highly hydrophobic membrane proteins. Studies involving mitochondrial translation have revealed numerous factors involved in mitoribosome biogenesis, including several uncharacterized components of the mitochondrial gene expression system. Mitochondrially encoded respiratory complexes subunits are translated and inserted into the mitochondrial inner membrane followed by proper association with nuclearly enconded auxiliary factors that are required for the formation of the holoenzyme. Here, we plan to investigate new uncharacterized factors with a putative role in regulatory events that lead to stoichiometry output of mitochondrially and nuclearly encoded components of the respiratory complexes. More specifically, the study of Cox1p haemylation and the identification of the specific role of uncharacterized factors (MRX) can provide new clues about the regulatory mechanisms pursued in this project. Due to the COVID-19 pandemic situation, in this project we aim to collaborate with global efforts in the investigation of mechanism of action of drugs that target mitochondria function, such as azythromycin. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRANCO, LETICIA VELOSO R.; SU, CHEN-HSIEN; TEIXEIRA, LORISA SIMAS; CHAGAS, JHULIA ALMEIDA CLARCK; BARROS, MARIO HENRIQUE; TZAGOLOFF, ALEXANDER. Allotopic expression of COX6 elucidates Atco-driven co-assembly of cytochrome oxidase and ATP synthase. LIFE SCIENCE ALLIANCE, v. 6, n. 11, p. 15-pg., 2023-11-01. (19/16015-3, 19/02799-2, 20/05812-7)

SANTOS, BARBARA; ZENG, RUI; JORGE, SASA F.; FERREIRA-JUNIOR, JOSE RIBAMAR; BARRIENTOS, ANTONI; BARROS, MARIO H.. Functional analyses of mitoribosome 54S subunit devoid of mitochondria-specific protein sequences. YEAST, NOV 2021. (13/07937-8, 20/05812-7, 18/03253-0, 17/23921-5)

CLARCK CHAGAS, JHULIA ALMEIDA; KFOURI MARTINS SOARES, MARIA ANTONIA; RIBEIRO FRANCO, LETICIA VELOSO; BARROS, MARIO H.. Overexpression of MRX9 impairs processing of RNAs encoding mitochondrial oxidative phosphorylation factors COB and COX1 in yeast. Journal of Biological Chemistry, v. 298, n. 8, p. 16-pg., 2022-07-21. (19/02799-2, 20/05812-7, 19/23984-2, 13/07937-8)