Molecular Connectivity of Mitochondrial Gene Expression and OXPHOS Biogenesis

Singh, Abeer Prakash; Salvatori, Roger; Aftab, Wasim; Aufschnaiter, Andreas; Carlström, Andreas; Forné, Ignasi; Imhof, Axel; Ott, Martin

doi:10.1016/j.molcel.2020.07.024

Cited by 52 publications

(54 citation statements)

References 98 publications

(118 reference statements)

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“…The Network graph in Fig. S1E was prepared with force directed layout in D3.js and R (Singh et al , 2020). The network graph in Fig.…”

Section: Methodsmentioning

confidence: 99%

The Integrity of the Speciation Core Complex is necessary for centromeric binding and reproductive isolation inDrosophila

Lukacs

Thomae

Krueger

et al. 2021

Preprint

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Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. We showed in the past that the expression levels of the two hybrid incompatibility factors Hmr and Lhr diverged in the two closely related Drosophila species, D. melanogaster and D. simulans, resulting in an increased level of both proteins in interspecies hybrids. This overexpression leads to mitotic defects, a misregulation in the expression of transposable elements and a decreased fertility. In this work, we describe a distinct six subunit Speciation Core Complex (SCC) containing HMR and LHR and analyse the effect of Hmr mutations on complex function and integrity. Our experiments suggest that HMR acts as a bridging factor between centromeric chromatin and pericentromeric heterochromatin, which is required for both its physiological function and its ability to cause hybrid male lethality.

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“…The Network graph in Fig. S1E was prepared with force directed layout in D3.js and R (Singh et al , 2020). The network graph in Fig.…”

Section: Methodsmentioning

confidence: 99%

The Integrity of the Speciation Core Complex is necessary for centromeric binding and reproductive isolation inDrosophila

Lukacs

Thomae

Krueger

et al. 2021

Preprint

Self Cite

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“…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 ). Prohibitins are thought to promote mETC assembly and quality control by assembling into inner membrane ring‐like scaffold structures that specify local protein and lipid composition ( Nijtmans et al, 2000 ; Singh et al, 2020 ).…”

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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“…Within the mitochondria, transcription and translation are tightly coupled presumably to make the mitochondrial gene expression more efficient and faster (Fontanesi, Soto et al, 2006, Kehrein, Schilling et al, 2015, Rodeheffer, Boone et al, 2001, Singh, Salvatori et al, 2020). Thus, diminished accumulation of mRNA levels in Δirc3ρ + could be indirect consequences of altered translation rates or vice versa .…”

Section: Resultsmentioning

confidence: 99%

IRC3regulates mitochondrial translation in response to metabolic cues inSaccharomyces cerevisiae

Kaur

Datta

2021

Preprint

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Mitochondrial oxidative phosphorylation (OXPHOS) enzymes are made up of dual genetic origin. Mechanism regulating expression of nuclear encoded OXPHOS subunits in response to metabolic cues (glucose vs. glycerol), is significantly understood while regulation of mitochondrially encoded OXPHOS subunits is poorly defined. Here, we show that IRC3 a DEAD/H box helicase, previously implicated in mitochondrial DNA maintenance, is central to integrating metabolic cues with mitochondrial translation. Irc3 associates with mitochondrial small ribosomal subunit in cells consistent with its role in regulating translation elongation based on Arg8m reporter system. Glucose grown Δirc3ρ+ and irc3 temperature sensitive cells at 37°C have reduced translation rates from majority of mRNAs. In contrast, when galactose was the carbon source, reduction in mitochondrial translation was observed predominantly from Cox1 mRNA in Δirc3ρ+ but no defect was observed in irc3 temperature sensitive cells, at 37°C. In support, of a model whereby IRC3 responds to metabolic cues, suppressors of Δirc3 isolated for restoration of growth on glycerol media restore mitochondrial translation differentially in presence of glucose vs. glycerol.

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Molecular Connectivity of Mitochondrial Gene Expression and OXPHOS Biogenesis

Cited by 52 publications

References 98 publications

The Integrity of the Speciation Core Complex is necessary for centromeric binding and reproductive isolation inDrosophila

The Integrity of the Speciation Core Complex is necessary for centromeric binding and reproductive isolation inDrosophila

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

IRC3regulates mitochondrial translation in response to metabolic cues inSaccharomyces cerevisiae

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