Rcf1 Modulates Cytochrome c Oxidase Activity Especially Under Energy-Demanding Conditions

Dawitz, Hannah; Schäfer, Jacob; Schaart, Judith M.; Magits, Wout; Brzezinski, Peter; Ott, Martin

doi:10.3389/fphys.2019.01555

Cited by 20 publications

(28 citation statements)

References 31 publications

(61 reference statements)

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“…Rcf dimerization could represent a way to shield the charged residues from the hydrophobic environment. In vivo, no Rcf1 dimers have been detected by crosslinking analysis [36]. However, we cannot exclude that Rcf proteins undergo conformational changes involving the flipping of the more hydrophilic C-terminal α-helix out of the inner membrane.…”

Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 90%

“…In addition, the respiratory growth defect of the ∆rcf1 strain is exacerbated under hypoxia, whereas the respiratory growth of the ∆cox13 strain is similar in the presence of 1% and 20% oxygen [20]. It is relevant in the context of stress that the ∆rcf1 strain, but not the ∆rcf2, is thermosensitive [36,50], a phenotype that could be related to the inner membrane protein organization/disorganization when the levels of SCs are decreased.…”

Section: Role Of Rcf Proteins Under Hypoxia and Oxidative Stressmentioning

confidence: 95%

“…Despite the association of Rcf1 with Cox3 from the early steps in CIV biogenesis to fully-assembled SCs, which is not a standard property for assembly factors, several lines of evidence argue against Rcf1 being a stoichiometric CIV structural component. Among them, Rcf1 is less abundant than CIV subunits in mitochondria, only a small fraction of Rcf1 interacts with CIV and SCs, and is specifically found in association with only a CIV subpopulation [36,51]. Instead, Rcf1 may act as a Cox3 chaperone required to promote its proper conformation, which in turn could affect the incorporation of the late assembly subunits Cox12 and Cox13 and/or the properties of the enzyme catalytic center [33,51].…”

Section: Role Of Rcf Proteins In Cytochrome C Oxidase Assembly and Fumentioning

confidence: 99%

“…The C-terminal portion of Rcf2, comprising two transmembrane α-helixes and a final C-terminal α-helix extending in the intermembrane space (IMS), has been identified in hypoxic respiratory SCs reconstructed by cryo-electron microscopy (cryo-EM) [34] (Figure 2b). The transmembrane portion of Rcf2, including the HIG1 domain [36,51], forms extensive interactions with the transmembrane domains of Cox3 and Cox13, whereas the IMS α-helix, a unique feature of yeast HIGD proteins, interacts with Cox12 [34]. The relevance of the conserved HIG1 domain for Rcf2 protein function is highlighted by the observations that the Rcf2 HIG1 domain alone can interact with SCs in isolated mitochondria [61], and the expression of a truncated Rcf1 protein containing just the HIG1 domain is sufficient to support respiratory growth [36].…”

Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 99%

“…The decrease of SC-associated Rcf2 in the absence of Rcf1 could be the consequence of the Rcf1-dependent CIV assembly defect. Indeed, the incorporation of Cox13 into CIV occurs before the binding of Rcf2 [20], and a small fraction of Rcf2 was detected co-sedimenting with Cox12-Cox13-containing CIV species upon extraction with the mild detergent digitonin [36,61], but not n-Dodecyl β-D-Maltoside (DDM) [19], suggesting a transient or labile interaction. The stable presence of Rcf2 in hypoxic SCs suggests that, at least under certain conditions, this protein may be a stable SC component required to modulate cytochrome c-mediated electron transfer of CIV enzymatic activity in response to the cellular energetic requirements [34].…”

Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 99%

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HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function

Timón‐Gómez

Bartley-Dier

Fontanesi

et al. 2020

Cells

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The biogenesis and function of eukaryotic cytochrome c oxidase or mitochondrial respiratory chain complex IV (CIV) undergo several levels of regulation to adapt to changing environmental conditions. Adaptation to hypoxia and oxidative stress involves CIV subunit isoform switch, changes in phosphorylation status, and modulation of CIV assembly and enzymatic activity by interacting factors. The latter include the Hypoxia Inducible Gene Domain (HIGD) family yeast respiratory supercomplex factors 1 and 2 (Rcf1 and Rcf2) and two mammalian homologs of Rcf1, the proteins HIGD1A and HIGD2A. Whereas Rcf1 and Rcf2 are expressed constitutively, expression of HIGD1A and HIGD2A is induced under stress conditions, such as hypoxia and/or low glucose levels. In both systems, the HIGD proteins localize in the mitochondrial inner membrane and play a role in the biogenesis of CIV as a free unit or as part as respiratory supercomplexes. Notably, they remain bound to assembled CIV and, by modulating its activity, regulate cellular respiration. Here, we will describe the current knowledge regarding the specific and overlapping roles of the several HIGD proteins in physiological and stress conditions.

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Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 90%

Section: Role Of Rcf Proteins Under Hypoxia and Oxidative Stressmentioning

confidence: 95%

Section: Role Of Rcf Proteins In Cytochrome C Oxidase Assembly and Fumentioning

confidence: 99%

Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 99%

Section: Role Of Rcf Proteins In Yeast Respiratory Supercomplex Biogementioning

confidence: 99%

See 3 more Smart Citations

HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function

Timón‐Gómez

Bartley-Dier

Fontanesi

et al. 2020

Cells

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The Diseased Mitoribosome

2020

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Mitochondria control life and death in eukaryotic cells. Harboring a unique circular genome, a by-product of an ancient endosymbiotic event, mitochondria maintains a specialized and evolutionary divergent protein synthesis machinery, the mitoribosome. Mitoribosome biogenesis depends on elements encoded in both the mitochondrial genome (the RNA components) and the nuclear genome (all ribosomal proteins and assembly factors). Recent cryo-EM structures of mammalian mitoribosomes have illuminated their composition and provided hints regarding their assembly and elusive mitochondrial translation mechanisms. A growing body of literature involves the mitoribosome in inherited primary mitochondrial disorders. Mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors impede mitoribosome biogenesis, causing protein synthesis defects that lead to respiratory chain failure and mitochondrial disorders such as encephalo-and cardiomyopathy, deafness, neuropathy, and developmental delays. In this article, we review the current fundamental understanding of mitoribosome assembly and function, and the clinical landscape of mitochondrial disorders driven by mutations in mitoribosome components and assembly factors, to portray how basic and clinical studies combined help us better understand both mitochondrial biology and medicine.

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Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae

Eldeeb,

Camacho Lopez,

Fontanesi

2024

IUBMB Life

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The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher‐order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high‐resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.

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Rcf1 Modulates Cytochrome c Oxidase Activity Especially Under Energy-Demanding Conditions

Cited by 20 publications

References 31 publications

HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function

HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function

The Diseased Mitoribosome

Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae

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