Timing of dimerization of the bc complex during mitochondrial respiratory chain assembly

Stephan, Katharina; Ott, Martin

doi:10.1016/j.bbabio.2020.148177

Cited by 24 publications

(24 citation statements)

References 36 publications

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“…The biogenesis of the mETC requires the concerted expression of nuclear and mitochondrial DNA (mtDNA) encoded genes and is highly regulated. Coordination of mETC subunits of dual origin occurs in part via the formation of modular intermediates within mitochondria that assemble sequentially into functional complexes ( Aich et al, 2018 ; Guerrero-Castillo et al, 2017 ; Lobo-Jarne et al, 2020 ; Ndi et al, 2018 ; Stephan and Ott, 2020 ; Van Vranken et al, 2015 ). Assembly of mETCs strategically occurs in specialized domains that link protein import, membrane insertion, and assembly machineries ( Singh et al, 2020 ; Stoldt et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

Vasseur

Friedman

Jost

et al. 2021

eLife

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Dysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified ovarian carcinoma immunoreactive antigen (OCIA) domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. We find that OCIAD1 is an inner mitochondrial membrane protein that forms a complex with supramolecular prohibitin assemblies. Our data indicate that OCIAD1 is required for maintenance of normal steady-state levels of Complex III and the proteolytic processing of the catalytic subunit cytochrome c1 (CYC1). In OCIAD1 depleted mitochondria, unprocessed CYC1 is hemylated and incorporated into Complex III. We propose that OCIAD1 acts as an adaptor within prohibitin assemblies to stabilize and/or chaperone CYC1 and to facilitate its proteolytic processing by the IMMP2L protease.

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Section: Introductionmentioning

confidence: 99%

Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

Vasseur

Friedman

Jost

et al. 2021

eLife

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“…Parallel to the coalescence of hemylated CYB with UQCRB and UQCRQ , matrix facing subunits UQCRC1 and UQCRC2 form a separate tetrameric module (i.e. a dimer of each), which is likely incorporated into the CYB -containing module simultaneously with CYC1 and UQCRH to yield the first dimeric intermediate of complex III, the pre-CIII 2 ( Figure 4 ) [ 181 ]. This step coincides with the dissociation of UQCC3, which may prevent the dimerisation of earlier intermediates [ 181 ].…”

Section: Introductionmentioning

confidence: 99%

“…a dimer of each), which is likely incorporated into the CYB -containing module simultaneously with CYC1 and UQCRH to yield the first dimeric intermediate of complex III, the pre-CIII 2 ( Figure 4 ) [ 181 ]. This step coincides with the dissociation of UQCC3, which may prevent the dimerisation of earlier intermediates [ 181 ]. Following dimerisation, the subunit UQCR10 is added to pre-CIII 2 [ 158 ].…”

Section: Introductionmentioning

confidence: 99%

Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome

Hock

Robinson

Stroud

2020

Biochemical Journal

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Mitochondria produce the bulk of the energy used by almost all eukaryotic cells through oxidative phosphorylation (OXPHOS) which occurs on the four complexes of the respiratory chain and the F1–F0 ATPase. Mitochondrial diseases are a heterogenous group of conditions affecting OXPHOS, either directly through mutation of genes encoding subunits of OXPHOS complexes, or indirectly through mutations in genes encoding proteins supporting this process. These include proteins that promote assembly of the OXPHOS complexes, the post-translational modification of subunits, insertion of cofactors or indeed subunit synthesis. The latter is important for all 13 of the proteins encoded by human mitochondrial DNA, which are synthesised on mitochondrial ribosomes. Together the five OXPHOS complexes and the mitochondrial ribosome are comprised of more than 160 subunits and many more proteins support their biogenesis. Mutations in both nuclear and mitochondrial genes encoding these proteins have been reported to cause mitochondrial disease, many leading to defective complex assembly with the severity of the assembly defect reflecting the severity of the disease. This review aims to act as an interface between the clinical and basic research underpinning our knowledge of OXPHOS complex and ribosome assembly, and the dysfunction of this process in mitochondrial disease.

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“…An alternative hypothesis is that CIII intermediates sequester CIV subunits when SC formation is impaired [ 131 ]. Importantly, it has been shown that dimerisation of two nascent CIII occurs during this stage [ 205 ].…”

Section: The Respiratory Chain and Supercomplexesmentioning

confidence: 99%

Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Needs

Protasoni

Henley

et al. 2021

Life

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The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease.

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Timing of dimerization of the bc complex during mitochondrial respiratory chain assembly

Cited by 24 publications

References 36 publications

Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome

Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

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