Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol

Klöppel, Christine; Suzuki, Yutaka; Kojer, Kerstin; Petrungaro, Carmelina; Longen, Sebastian; Fiedler, Sebastian; Keller, Sandro; Riemer, Jan

doi:10.1091/mbc.e11-04-0293

Cited by 57 publications

(51 citation statements)

References 28 publications

(55 reference statements)

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“…As all other folding enzymes, Mia40 does not provide specific folding information. It facilitates the folding of many different proteins, also of proteins that do not contain helices with twin CX 9 C or twin CX 3 C motifs and MISS/ITS sequences [32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

“…Sulphur atoms of the structural disulphides are coloured yellow, cysteines are numbered according to the amino-acid sequence. The first CX 9 C motif is coloured purple (residues [26][27][28][29][30][31][32][33], the second CX 9 C motif (residues 47-57) is magenta and the hydrophobic residues 37-39 following Cys36 are blue. The residues of the MISS/ITS sequence (F50, I51, Y54) and I37, L38, F39 are shown in ball and sticks representation.…”

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confidence: 99%

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Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

Koch

Schmid

2014

Nat Commun

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Mia40 catalyses the oxidative folding of disulphide-containing proteins in the mitochondria. The folding pathway is directed by the formation of the first mixed disulphide between Mia40 and its substrate. Here, we employ Cox17 to elucidate the molecular determinants of this reaction. Mia40 engages initially in a dynamic non-covalent enzyme-substrate complex that forms and dissociates within milliseconds. Cys36 of Cox17 forms the mixed disulphide in an extremely rapid reaction that is limited by the preceding complex formation with Mia40. Cys36 reacts much faster than the three other cysteines of Cox17, because it neighbours three hydrophobic residues. Mia40 binds preferentially to hydrophobic regions and the dynamic nature of the non-covalent complex allows rapid reorientation for an optimal positioning of the reactive cysteine. Mia40 thus uses the unique proximity between its substrate-binding site and the catalytic disulphide to select a particular cysteine for forming the critical initial mixed disulphide.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

Koch

Schmid

2014

Nat Commun

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“…Although these residues are not the CX 3 C or CX 9 C motifs characteristic of most MIA substrates (3,4), emerging data indicate that substrates that have CX 2 C and other arrangements of cysteine residues (e.g., Erv1, Ccs1) use the MIA pathway for import into the intermembrane space (40)(41)(42). An alternative pathway would be driven by cytochrome heme lyases (e.g., Cyt2 and Cyc3), by analogy with the pathway for cytochrome c that is driven by the heme lyase Cyc3.…”

Section: Discussionmentioning

confidence: 99%

A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways

Hewitt¹,

Heinz

Shingú-Vázquez³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The controlled biogenesis of mitochondria is a key cellular system coordinated with the cell division cycle, and major efforts in systems biology currently are directed toward understanding of the control points at which this coordination is achieved. Here we present insights into the function, evolution, and regulation of mitochondrial biogenesis through the study of the protein import machinery in the human fungal pathogen, Candida albicans. Features that distinguish C. albicans from baker's yeast (Saccharomyces cerevisiae) include the stringency of metabolic control at the level of oxygen consumption, the potential for ATP exchange through the porin in the outer membrane, and components and domains in the sorting and assembling machinery complex, a molecular machine that drives the assembly of proteins in the outer mitochondrial membrane. Analysis of targeting sequences and assays of mitochondrial protein import show that components of the electron transport chain are imported by distinct pathways in C. albicans and S. cerevisiae, representing an evolutionary rewiring of mitochondrial import pathways. We suggest that studies using this pathogen as a model system for mitochondrial biogenesis will greatly enhance our knowledge of how mitochondria are made and controlled through the course of the cell-division cycle.SAM complex | Omp85 | stop-transfer pathway | Sam51

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“…Depletion of Mia40 did not affect the mitochondrial levels of LtErv but resulted in reduced levels of known import substrates of Mia40 including ScErv1, Ccs1, and Tim13 (Fig. 2E) (41)(42)(43)(44)(45). Other mitochondrial proteins, such as the matrix proteins Tim44 and Hep1, were not affected by the depletion of Mia40 (Fig.…”

Section: Kinetoplastid Erv Homologues Have Altered Domainmentioning

confidence: 95%

Divergent Molecular Evolution of the Mitochondrial Sulfhydryl:Cytochrome c Oxidoreductase Erv in Opisthokonts and Parasitic Protists

Eckers

Petrungaro

Groß

et al. 2013

Journal of Biological Chemistry

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Background:The machinery for protein import into the mitochondrial intermembrane space has been studied in mammals, yeast, and plants. Results: Protist Erv homologues are conserved sulfhydryl:cytochrome c oxidoreductases with altered mechanisms. Conclusion:The composition and mechanism of the mitochondrial protein import machinery differs between eukaryotic lineages. Significance: The current knowledge on mitochondrial protein import cannot be generally transferred to all eukaryotes.

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Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol

Cited by 57 publications

References 28 publications

Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways

Divergent Molecular Evolution of the Mitochondrial Sulfhydryl:Cytochrome c Oxidoreductase Erv in Opisthokonts and Parasitic Protists

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