Rcf proteins and their differential specificity for respiratory chain complexes: A unique role for Rcf2 on oxygen sensitive supercomplexes?

TY - JOUR

T1 - Rcf proteins and their differential specificity for respiratory chain complexes: A unique role for Rcf2 on oxygen sensitive supercomplexes?

AU - Homberg, Bettina

AU - Römpler, Katharina

AU - Wissel, Mirjam

AU - Callegari, Sylvie

AU - Deckers, Markus

N1 - Copyright © 2021 Elsevier B.V. All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - The respiratory chain, embedded in the inner mitochondrial membrane, is organized as a network of individual complexes, as well as large supercomplex structures. In the yeast S. cerevisiae, these supercomplexes consist of a dimeric cytochrome bc1-complex adjoined by one or two copies of cytochrome c oxidase. The formation of these complexes is a dynamic process and is regulated by various factors in order to adapt to environmental and metabolic changes. These adaptions occur at the level of enzyme regulation, complex assembly, as well as altered nuclear and mitochondrial transcription and translation. Members of the Rcf protein family (Rcf1, Rcf2 and Rcf3) are required for respiratory complex biogenesis and act mainly by regulating the assembly and enzyme activity of complex IV within supercomplexes. Rcf1 functions in the assembly process via the COX3 module, whereas Rcf2 and Rcf3 are responsible for enzymatic regulation. In this study, we have extended this knowledge to show that Rcf2 and Rcf3 can also associate with newly synthesized mitochondrial encoded proteins, such as Cox3, and therefore contribute to complex IV assembly. Since the Rcf proteins have overlapping regions of sequence similarities, we engineered novel fusion proteins of Rcf1 and Rcf3, with parts of Rcf2, to probe which of the Rcf protein domains can be attributed to their functions. The fusion proteins could compensate for the individual phenotypes of the complexIV assembly defect and the lack of complex IV regulation. Finally, the role of Rcf proteins for defined species of respiratory chain complexes in a hypoxic model was investigated, uncovering a unique association of Rcf2 with the hypoxic III2IV supercomplex. We therefore suggest an involvement of Rcf2 for adaption of the respiratory chain to altering oxygen levels.

AB - The respiratory chain, embedded in the inner mitochondrial membrane, is organized as a network of individual complexes, as well as large supercomplex structures. In the yeast S. cerevisiae, these supercomplexes consist of a dimeric cytochrome bc1-complex adjoined by one or two copies of cytochrome c oxidase. The formation of these complexes is a dynamic process and is regulated by various factors in order to adapt to environmental and metabolic changes. These adaptions occur at the level of enzyme regulation, complex assembly, as well as altered nuclear and mitochondrial transcription and translation. Members of the Rcf protein family (Rcf1, Rcf2 and Rcf3) are required for respiratory complex biogenesis and act mainly by regulating the assembly and enzyme activity of complex IV within supercomplexes. Rcf1 functions in the assembly process via the COX3 module, whereas Rcf2 and Rcf3 are responsible for enzymatic regulation. In this study, we have extended this knowledge to show that Rcf2 and Rcf3 can also associate with newly synthesized mitochondrial encoded proteins, such as Cox3, and therefore contribute to complex IV assembly. Since the Rcf proteins have overlapping regions of sequence similarities, we engineered novel fusion proteins of Rcf1 and Rcf3, with parts of Rcf2, to probe which of the Rcf protein domains can be attributed to their functions. The fusion proteins could compensate for the individual phenotypes of the complexIV assembly defect and the lack of complex IV regulation. Finally, the role of Rcf proteins for defined species of respiratory chain complexes in a hypoxic model was investigated, uncovering a unique association of Rcf2 with the hypoxic III2IV supercomplex. We therefore suggest an involvement of Rcf2 for adaption of the respiratory chain to altering oxygen levels.

KW - Electron Transport Complex IV/genetics

KW - Oxidative Phosphorylation

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins/genetics

U2 - 10.1016/j.bbamcr.2021.119133

DO - 10.1016/j.bbamcr.2021.119133

M3 - SCORING: Journal article

C2 - 34450214

VL - 1868

JO - BBA-MOL CELL RES

JF - BBA-MOL CELL RES

SN - 0167-4889

IS - 12

M1 - 119133

ER -