Assembly of the mitochondrial membrane system. Characterization of nuclear mutants of Saccharomyces cerevisiae with defects in mitochondrial ATPase and respiratory enzymes.

Tzagoloff, Alexander; Akai, Anna; Needleman, RB

doi:10.1016/s0021-9258(19)40840-5

Cited by 247 publications

(22 citation statements)

References 21 publications

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“…Proteins in the coenzyme Q (CoQ) biosynthetic pathway form a complex associated with the mitochondrial inner membrane and synthesize a highly hydrophobic prenylated benzoquinone lipid that is an essential component of the respiratory chain (Stefely and Pagliarini, 2017;Awad et al, 2018). The CoQ lipid functions to transfer electrons from respiratory complexes I and II to complex III and facilitates H + pumping across the inner membrane to power ATP synthesis by Complex V. Essential components of the CoQ biosynthetic pathway are highly conserved across kingdoms and, in yeast, are required for growth on nonfermentable carbon sources, consistent with the essential role of CoQ in respiration (Tzagoloff et al, 1975;Tzagoloff and Dieckmann, 1990). In humans, mutations in genes required for CoQ synthesis cause heterogeneous phenotypes consistent with mitochondrial respiratory chain deficiency (Luna-Sánchez et al, 2015;Acosta et al, 2016).…”

Section: Introductionmentioning

confidence: 65%

Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts

Subramanian

Jochem

Vasseur

et al. 2019

Journal of Cell Biology

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Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane–associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenzoate head-to-tail attachment, and head modification, resulting in the production of CoQ. In yeast, we discovered that head-modifying CoQ pathway components selectively colocalize to multiple resolvable domains in vivo, representing supramolecular assemblies. In cells engineered with conditional ON or OFF CoQ pathways, domains were strictly correlated with CoQ production and substrate flux, respectively, indicating that CoQ lipid intermediates are required for domain formation. Mitochondrial CoQ domains were also observed in human cells, underscoring their conserved functional importance. CoQ domains within cells were highly enriched adjacent to ER–mitochondria contact sites. Together, our data suggest that CoQ domains function to facilitate substrate accessibility for processive and efficient CoQ production and distribution in cells.

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Section: Introductionmentioning

confidence: 65%

Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts

Subramanian

Jochem

Vasseur

et al. 2019

Journal of Cell Biology

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“…1) derives from the characterization of accumulating Q biosynthetic intermediates in Q-deficient mutant strains of Escherichia coli and Saccharomyces cerevisiae (10,11). Q mutant strains of S. cerevisiae are non-respiring or petite mutants (12,13) and have been classified into eight complementation groups, coq1-coq8 (14). Addition of Q 2 or Q 6 to mitochondrial extracts prepared from each coq mutant restored NADH-cytochrome c reductase activity to levels near that of the wild-type parental strain (12).…”

Section: Ubiquinone (Coenzyme Q) Is a Lipid That Transports Electrons In The Respiratory Chains Of Both Prokaryotes And Eukaryotes Mutantmentioning

confidence: 99%

“…Q mutant strains of S. cerevisiae are non-respiring or petite mutants (12,13) and have been classified into eight complementation groups, coq1-coq8 (14). Addition of Q 2 or Q 6 to mitochondrial extracts prepared from each coq mutant restored NADH-cytochrome c reductase activity to levels near that of the wild-type parental strain (12). Three of the complementation groups (coq1-coq3) have been characterized.…”

Section: Ubiquinone (Coenzyme Q) Is a Lipid That Transports Electrons In The Respiratory Chains Of Both Prokaryotes And Eukaryotes Mutantmentioning

confidence: 99%

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

Marbois

Clarke

1996

Journal of Biological Chemistry

177

159

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Ubiquinone (coenzyme Q) is a lipid that transports electrons in the respiratory chains of both prokaryotes and eukaryotes. Mutants of Saccharomyces cerevisiae deficient in ubiquinone biosynthesis fail to grow on nonfermentable carbon sources and have been classified into eight complementation groups (coq1 coq8; Tzagoloff, A., and Dieckmann, C. L.(1990) Microbiol. Rev. 54, 211-225). In this study we show that although yeast coq7 mutants lack detectable ubiquinone, the coq7 1 mutant does synthesize demethoxyubiquinone (2-hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinone), a ubiquinone biosynthetic intermediate. The corresponding wild-type COQ7 gene was isolated, sequenced, and found to restore growth on nonfermentable carbon sources and the synthesis of ubiquinone. The sequence predicts a polypeptide of 272 amino acids which is 40% identical to a previously reported Caenorhabditis elegans open reading frame. Deletion of the chromosomal COQ7 gene generates respiration defective yeast mutants deficient in ubiquinone. Analysis of several coq7 deletion strains indicates that, unlike the coq7 1 mutant, demethoxyubiquinone is not produced. Both coq7 1 and coq7 deletion mutants, like other coq mutants, accumulate an early intermediate in the ubiquinone biosynthetic pathway, 3-hexaprenyl-4-hydroxybenzoate. The data suggest that the yeast COQ7 gene may encode a protein involved in one or more monoxygenase or hydroxylase steps of ubiquinone biosynthesis.

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“…Mitochondrial isolation, protein determination and SDS-PAGE were performed as previously described (Dienhart and Stuart, 2008). Spectral measurements of specific enzyme activities of the cytochrome bc 1 and COX complexes were performed as previously described (Tzagoloff et al, 1975) and citrate synthase was measured according to the Sigma-Aldrich protocol (MAK057) with the exception that isolated mitochondria were solubilized in 0.1M Tris-HCl with 1 mM DDM, pH 8.1, at a concentration of 1.6 μg/μL prior to enzyme determinations. BN-PAGE analysis was performed essentially as described previously (Box et al, 2017).…”

Section: Miscellaneousmentioning

confidence: 99%

The mitospecific domain of Mrp7 (bL27) supports mitochondrial translation during fermentation and is required for effective adaptation to respiration

Anderson

Box

Stuart

2022

MBoC

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We demonstrate here that mitoribosomal protein synthesis, responsible for the synthesis of oxidative phosphorylation (OXPHOS) subunits encoded by mitochondrial genome, occurs at high levels during glycolysis fermentation and in a manner uncoupled from OXPHOS complex assembly regulation. Furthermore, we provide evidence that the mitospecific domain of Mrp7 (bL27), a mitoribosomal component, is required to maintain mitochondrial protein synthesis during fermentation, but is not required under respiration growth conditions. Maintaining mitotranslation under high glucose fermentation conditions also involves Mam33 (p32/gC1qR homolog), a binding partner of Mrp7’s mitospecific domain, and together they confer a competitive advantage for a cell's ability to adapt to respiration-based metabolism when glucose becomes limiting. Furthermore, our findings support that the mitoribosome, and specifically the central protuberance (CP) region, may be differentially regulated and/or assembled, under the different metabolic conditions of fermentation and respiration. Based on our findings, we propose the purpose of mitotranslation is not limited to the assembly of OXPHOS complexes, but also plays a role in mitochondrial signaling critical for switching cellular metabolism from a glycolysis- to a respiratory-based state.

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Assembly of the mitochondrial membrane system. Characterization of nuclear mutants of Saccharomyces cerevisiae with defects in mitochondrial ATPase and respiratory enzymes.

Cited by 247 publications

References 21 publications

Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts

Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

The mitospecific domain of Mrp7 (bL27) supports mitochondrial translation during fermentation and is required for effective adaptation to respiration

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