Factors Controlling the Uptake of Yeast Copper/Zinc Superoxide Dismutase into Mitochondria*

@article{Field2003FactorsCT,
  title={Factors Controlling the Uptake of Yeast Copper/Zinc Superoxide Dismutase into Mitochondria*},
  author={Lori Sturtz Field and Yoshiaki Furukawa and Thomas V. O’Halloran and Valeria C Culotta},
  journal={Journal of Biological Chemistry},
  year={2003},
  volume={278},
  pages={28052 - 28059}
}
We have previously shown that a fraction of yeast copper/zinc-superoxide dismutase (SOD1) and its copper chaperone CCS localize to the intermembrane space of mitochondria. In the present study, we have focused on the mechanism by which SOD1 is partitioned between cytosolic and mitochondrial pools. Using in vitro mitochondrial import assays, we show that only a very immature form of the SOD1 polypeptide that is apo for both copper and zinc can efficiently enter the mitochondria. Moreover, a… 
Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria.
TLDR
It is found that the physiological regulation of mitochondrial localization is either inefficient or absent in SOD1 pathogenic mutants, and it is proposed that misfolding and aggregation of these mutants that trap them inside mitochondria.
Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria.
TLDR
CCS1 serves as a specialized import receptor in mitochondria that facilitates the import and folding of SOD1 and CCS1, thereby extending the substrate spectrum of oxidation-dependent protein import in the mitochondrial intermembrane space.
Mechanisms of Biosynthesis of Mammalian Copper/Zinc Superoxide Dismutase*
TLDR
The data provide a cell biological model of SOD1 biosynthesis that is consistent with the concept of limited intracellular copper availability and indicate that the metallochaperone CCS is a critical determinant of S OD1 activity in mammalian cells.
Activation of Cu,Zn-Superoxide Dismutase in the Absence of Oxygen and the Copper Chaperone CCS*
TLDR
The CCS-independent pathway is able to activate SOD1s even under anaerobic conditions, and Cu,Zn-SOD from metazoans may retain activity over a wide range of physiological oxygen tensions.
Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space.
TLDR
Mutant SOD1 localization and aggregation in the IMS might cause the mitochondrial abnormalities observed in familial ALS and could play a significant role in disease pathogenesis.
Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone.
TLDR
It is demonstrated here that the CCS-independent activation of mammalian SOD1 involves glutathione, particularly the reduced form, or GSH, which was seen with human S OD1 molecules that were expressed in either yeast cells or immortalized fibroblasts.
Mitochondrial Matrix Copper Complex Used in Metallation of Cytochrome Oxidase and Superoxide Dismutase*
TLDR
It is suggested that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS.
Effects of VDAC isoforms on CuZn-superoxide dismutase activity in the intermembrane space of Saccharomyces cerevisiae mitochondria.
TLDR
Using Saccharomyces cerevisiae mutants depleted of either isoform of VDAC, it is shown that the activity of IMS CuZnSOD coincides with the presence of a given VDac isoform and changes in a growth phase dependent way.
Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1
TLDR
Novel mitochondrial players that are possibly involved in pathological conditions caused by changes in the biogenesis of Sod1 are identified, including yeast mutants with mutations in highly conserved amino acid residues corresponding to human mutations that cause amyotrophic lateral sclerosis.
Yeast Contain a Non-proteinaceous Pool of Copper in the Mitochondrial Matrix*
The yeast mitochondrion is shown to contain a pool of copper that is distinct from that associated with the two known mitochondrial cuproenzymes, superoxide dismutase (Sod1) and cytochrome c oxidase
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TLDR
It is demonstrated that Cu,Zn-SOD1 in the mitochondria appears important for reactive oxygen physiology and may have critical implications for SOD1 mutations linked to the fatal neurodegenerative disorder, amyotrophic lateral sclerosis.
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TLDR
It is demonstrated here that the delivery of copper to copper/zinc superoxide dismutase (SOD1) is mediated through a soluble factor identified as Saccharomyces cerevisiae LYS7 and human CCS (copperchaperone for SOD).
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TLDR
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TLDR
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TLDR
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TLDR
It is demonstrated here that this process involves the cooperation of three distinct regions of the copper chaperone for SOD1 (CCS): an amino-terminal Domain I homologous to the Atx1p metallochaperone, a central portion (Domain II) homologicous to S OD1, and a short carboxyl- terminal peptide unique to CCS molecules (Domain III).
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TLDR
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TLDR
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TLDR
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