The Conserved Mitochondrial Twin Cx9C Protein Cmc2 Is a Cmc1 Homologue Essential for Cytochrome c Oxidase Biogenesis

Horn, Darryl; Zhou, Wen; Trevisson, Eva; Al-Ali, Hassan; Harris, Thomas K.; Salviati, Leonardo; Barrientos, Antoni

doi:10.1074/jbc.m110.104786

Cited by 37 publications

(38 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the precise mechanisms for these pleiotropic effects remain to be explored, they were similar to the alterations measured in a ⌬cox14 strain (Fig. 2D) and several other COX assembly mutants (29).…”

Section: Resultsmentioning

confidence: 61%

Cox25 Teams Up with Mss51, Ssc1, and Cox14 to Regulate Mitochondrial Cytochrome c Oxidase Subunit 1 Expression and Assembly in Saccharomyces cerevisiae

Fontanesi¹,

Clemente

Barrientos

2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

In the yeast Saccharomyces cerevisiae, mitochondrial cytochrome c oxidase (COX) biogenesis is translationally regulated. Mss51, a specific COX1 mRNA translational activator and Cox1 chaperone, drives the regulatory mechanism. During translation and post-translationally, newly synthesized Cox1 physically interacts with a complex of proteins involving Ssc1, Mss51, and Cox14, which eventually hand over Cox1 to the assembly pathway. This step is probably catalyzed by assembly chaperones such as Shy1 in a process coupled to the release of Ssc1-Mss51 from the complex. Impaired COX assembly results in the trapping of Mss51 in the complex, thus limiting its availability for COX1 mRNA translation. An exception is a null mutation in COX14 that does not affect Cox1 synthesis because the Mss51 trapping complexes become unstable, and Mss51 is readily available for translation. Here we present evidence showing that Cox25 is a new essential COX assembly factor that plays some roles similar to Cox14. A null mutation in COX25 by itself or in combination with other COX mutations does not affect Cox1 synthesis. Cox25 is an inner mitochondrial membrane intrinsic protein with a hydrophilic C terminus protruding into the matrix. Cox25 is an essential component of the complexes containing newly synthesized Cox1, Ssc1, Mss51, and Cox14. In addition, Cox25 is also found to interact with Shy1 and Cox5 in a complex that does not contain Mss51. These results suggest that once Ssc1-Mss51 are released from the Cox1 stabilization complex, Cox25 continues to interact with Cox14 and Cox1 to facilitate the formation of multisubunit COX assembly intermediates.

show abstract

Section: Resultsmentioning

confidence: 61%

Cox25 Teams Up with Mss51, Ssc1, and Cox14 to Regulate Mitochondrial Cytochrome c Oxidase Subunit 1 Expression and Assembly in Saccharomyces cerevisiae

Fontanesi¹,

Clemente

Barrientos

2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Two strains that showed a strong respiratory growth stimulation by GSH and DTT caught our attention because they lacked genes for the ''twin Cx 9 C'' proteins Cmc1 and Coa4, which were shown before to play a role in the biogenesis of cytochrome c oxidase (7,22,23,32). These strains showed no (Dcmc1) or poor (Dcoa4) growth on glycerol but were strongly stimulated by either GSH or DTT.…”

Section: Reductants Suppress the Growth Defect Of Mutants Lacking Cmcmentioning

confidence: 99%

“…It was previously demonstrated that Cmc1 and Coa4 play a direct or indirect role in the assembly of cytochrome c oxidase (7,22,23). We therefore analyzed the activity of cytochrome c oxidase in Dcmc1 and Dcoa4 mitochondria (Fig.…”

Section: Mutants Lacking Cmc1 or Coa4 Show Reduced Levels Of Cytochromentioning

confidence: 99%

Inaccurately Assembled CytochromecOxidase Can Lead to Oxidative Stress-Induced Growth Arrest

Bode

Longen

Morgan

et al. 2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: To identify yeast mutants that show a strong redox dependence of the ability to respire, we systematically screened a yeast deletion library for mutants that require the presence of reductants for growth on nonfermentable carbon sources. Results: Respirative growth of 44 yeast mutants was significantly improved by the addition of dithiothreitol or glutathione. Two mutants that were strongly stimulated by reductants lacked the proteins Cmc1 and Coa4. Both proteins belong to the family of ''twin Cx 9 C'' proteins present in the intermembrane space of mitochondria. Deletion of CMC1 or COA4 leads to assembly defects of cytochrome c oxidase, in particular to the lack of Cox1 and rapid degradation of Cox2 and Cox3. Interestingly, the presence of the reductants does not suppress these assembly defects and the levels of cytochrome c oxidase remain reduced. Reductants and antioxidants such as ascorbic acid rather counteract the effects of hydrogen peroxide that is produced from partially assembled cytochrome c oxidase intermediates. Innovation: Here we show that oxidative stress generated by the accumulation of partially assembled respiratory chain complexes prevents growth on carbon sources that force cells to respire. Conclusion: Defects in the assembly of cytochrome c oxidase can lead to increased production of hydrogen peroxide, which is sensed in cells and blocks their proliferation. We propose that this redox-regulated feedback regulation specifically slows down the propagation of cells carrying respiratory chain mutations in order to select for cells of high mitochondrial fitness. Antioxid. Redox Signal. 18, 1597-1612.

show abstract

“…Cox19 and Cox23, which are structurally related to Cox17, are also involved in copper delivery, although they may not bind copper directly (72,73). Likewise, the proteins Cmc1 and Cmc2 have recently been shown to be involved in the maturation of cytochrome c oxidase (74,75).…”

Section: Substrates Of Mitochondrial Disulfide Relaymentioning

confidence: 99%

Mitochondrial Disulfide Relay: Redox-regulated Protein Import into the Intermembrane Space

Herrmann

Riemer

2012

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

99% of all mitochondrial proteins are synthesized in the cytosol, from where they are imported into mitochondria. In contrast to matrix proteins, many proteins of the intermembrane space (IMS) lack presequences and are imported in an oxidation-driven reaction by the mitochondrial disulfide relay. Incoming polypeptides are recognized and oxidized by the IMSlocated receptor Mia40. Reoxidation of Mia40 is facilitated by the sulfhydryl oxidase Erv1 and the respiratory chain. Although structurally unrelated, the mitochondrial disulfide relay functionally resembles the Dsb (disufide bond) system of the bacterial periplasm, the compartment from which the IMS was derived 2 billion years ago.Mitochondria consist of two aqueous compartments, the matrix and the intermembrane space (IMS).2 The mitochondrial genome codes only for roughly a dozen different proteins, and the vast majority of mitochondrial proteins are nuclear encoded. Even simple organisms such as bakers' yeast contain several hundred matrix proteins. Matrix proteins are synthesized in the cytosol as precursors with N-terminal presequences (also referred to as matrix-targeting signals), which are processed following translocation. The import of matrix-destined preproteins is mediated by translocases in the outer membrane (TOM complex) and inner membrane (TIM23 complex) in an ATP-and membrane potential-dependent process (for review, see Refs. 1-3). Proteomic studies suggest that positively charged presequences are consistently found on all matrix proteins, although in some cases they are not proteolytically removed (4, 5).So far, ϳ50 different proteins were identified in the IMS of yeast mitochondria, and the list of IMS proteins is rapidly growing (6). The functions of these proteins are diverse. In addition to components involved in mitochondrial respiration, the IMS contains many proteins that transport proteins, metabolites, lipids, or metal ions between both mitochondrial membranes. In addition, several pro-apoptotic components are stored in the IMS and released when the cell death program is triggered (7).Some IMS proteins are synthesized in the cytosol as preproteins carrying bipartite presequences that consist of a matrixtargeting signal followed by a hydrophobic sorting region. The latter serves as a stop-transfer sequence that is inserted into the inner membrane during protein import and removed by IMSlocated proteases (8). Proteins with bipartite presequences embark on the general matrix-directed protein-targeting pathway, from which they are redirected into the IMS. However, many IMS proteins lack N-terminal targeting signals and are sorted into the IMS on a unique import route that differs in many respects from the matrix-targeting pathway. Import of many of these proteins relies on the mitochondrial disulfide relay, which is introduced below. Mitochondrial Disulfide Relay: Mia40 and Erv1The IMS proteins Mia40 (mitochondrial IMS import and assembly pathway 40 kDa) and Erv1 (essential for respiratory growth and viability 1) represent the central com...

show abstract

The Conserved Mitochondrial Twin Cx9C Protein Cmc2 Is a Cmc1 Homologue Essential for Cytochrome c Oxidase Biogenesis

Cited by 37 publications

References 54 publications

Cox25 Teams Up with Mss51, Ssc1, and Cox14 to Regulate Mitochondrial Cytochrome c Oxidase Subunit 1 Expression and Assembly in Saccharomyces cerevisiae

Cox25 Teams Up with Mss51, Ssc1, and Cox14 to Regulate Mitochondrial Cytochrome c Oxidase Subunit 1 Expression and Assembly in Saccharomyces cerevisiae

Inaccurately Assembled CytochromecOxidase Can Lead to Oxidative Stress-Induced Growth Arrest

Mitochondrial Disulfide Relay: Redox-regulated Protein Import into the Intermembrane Space

Contact Info

Product

Resources

About