ATCO1, a mitochondrial master regulator of ATP Synthase and Cytochrome Oxidase biogenesis?

• Grant number: 19/16015-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 15, 2019
• End date: November 14, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mario Henrique de Barros
• Grantee: Leticia Veloso Ribeiro Franco
• Supervisor: Alexander A Tzagoloff
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Columbia University in the City of New York, United States
• Associated to the scholarship: 19/02799-2 - ATCO1, a mitochondrial master regulator of ATP synthase and cytochrome oxidase biogenesis?, BP.PD

Abstract

Fungal and mammalian ATP Synthase and Cytochrome c oxidase (COX) are examples ofmitochondrial hetero-oligomeric complexes whose assembly depends on the expression ofmitochondrial and nuclear genes. In prior studies, yeast ATP synthase was shown to be assembledfrom three modules, each formed by a separate pathway. The simplest module is a ring, which inyeast consists of 10 identical copies of mitochondrially encoded Atp9 (homolog of bacterial Csubunit). The ring is an important structural and functional component of the rotor in F-, V- andA- type ATPases and functions to either use a proton gradient to form the phosphodiester bond ofATP or hydrolyze ATP to generate a proton gradient. Nascent Atp9, not yet assembled into thering, was recently found to be physically associated with Cox6 (subunit of COX encoded by thenuclear DNA) in high molecular weight complexes named ATCO1 (ATP synthase and COX). Ourexperiments indicate that ATCO1 is a source of Atp9 for ATP synthase assembly. This evidenceprovides the basis for the hypothesis that one of the functions of ATCO1 is to confer an adequatestoichiometry of ATP synthase and COX for their function in oxidative phosphorylation. The mainobjective of this project is to verify experimentally the role of ATCO1 in coordinating assemblyof 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 themitochondrial respiratory chain is assembled and how this process is regulated.

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)

RIBEIRO FRANCO, LETICIA VELOSO; SU, CHEN HSIEN; TZAGOLOFF, ALEXANDER. Modular assembly of yeast mitochondrial ATP synthase and cytochrome oxidase. Biological Chemistry, v. 401, n. 6-7, p. 835-853, MAY 2020. (19/16015-3)

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)