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ATCO1, a mitochondrial master regulator of ATP synthase and cytochrome oxidase biogenesis?

Grant number: 19/02799-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): May 01, 2019
Effective date (End): January 16, 2024
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Mario Henrique de Barros
Grantee:Leticia Veloso Ribeiro Franco
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):19/16015-3 - ATCO1, a mitochondrial master regulator of ATP Synthase and Cytochrome Oxidase biogenesis?, BE.EP.PD


Fungal and mammalian ATP Synthase and Cytochrome C oxidase (COX) are examples of mitochondrial hetero-oligomeric complexes whose assembly depends on the expression of mitochondrial and nuclear genes. In prior studies, yeast ATP synthase was shown to be assembled from three modules, each formed by a separate pathway. The simplest module is a ring, which in yeast consists of 10 identical copies of mitochondrially encoded Atp9 (homolog of bacterial C subunit). The ring is an important structural and functional component of the rotor in F-, V- and A- type ATPases and functions to either use a proton gradient to form the phosphodiester bond of ATP or hydrolyze ATP to generate a proton gradient. Nascent Atp9, not yet assembled into the ring, was recently found to be physically associated with Cox6 (subunit of COX encoded by the nuclear DNA) in high molecular weight complexes named ATCO1 (ATP synthase and COX). Our experiments indicate that ATCO1 is a source of Atp9 for ATP synthase assembly. This evidence provides the basis for the hypothesis that one of the functions of ATCO1 is to confer an adequate stoichiometry of ATP synthase and COX for their function in oxidative phosphorylation. The main objective of this project is to verify experimentally the role of ATCO1 in coordinating assembly of ATP synthase and COX. We will also determine if ATCO1 is present in human mitochondria. The studies on the novel ATCO1 complex will increase our understanding of how the mitochondrial respiratory chain is assembled and how this process is regulated. (AU)

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Scientific publications (4)
(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)
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., . (19/02799-2, 20/05812-7, 19/23984-2, 13/07937-8)
RIBEIRO FRANCO, LETICIA VELOSO; SU, CHEN-HSIEN; BURNETT, JULIA; TEIXEIRA, LORISA SIMAS; TZAGOLOFF, ALEXANDER. Atco, a yeast mitochondrial complex of Atp9 and Cox6, is an assembly intermediate of the ATP synthase. PLoS One, v. 15, n. 5, . (19/02799-2)
FRANCO, LETICIA V. R.; BREMNER, LUCA; BARROS, MARIO H.. Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies of Saccharomyces cerevisiae. LIFE-BASEL, v. 10, n. 11, . (19/02799-2)
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., . (19/16015-3, 19/02799-2, 20/05812-7)

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