Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria

Lori Sturtz Field, Yoshiaki Furukawa, Thomas V. O'Halloran, Valeria Cizewski Culotta

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

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 conserved disulfide in SOD1 that is essential for activity must be reduced to facilitate mitochondrial uptake of SOD1. Once inside the mitochondria, SOD1 is converted to an active holo enzyme through the same post-translational modifications seen with cytosolic SOD1. The presence of high levels of CCS in the mitochondrial intermembrane space results in enhanced mitochondrial accumulation of SOD1, and this apparently involves CCS-mediated retention of SOD1 within mitochondria. This retention of SOD1 is not dependent on copper loading of the enzyme but does require protein-protein interactions at the heterodimerization interface of SOD1 and CCS as well as conserved cysteine residues in both molecules. A model for how CCS-mediated post-translational modification of SOD1 controls its partitioning between the mitochondria and cytosol will be presented.

Original languageEnglish
Pages (from-to)28052-28059
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number30
DOIs
Publication statusPublished - 2003 Jul 25
Externally publishedYes

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Mitochondria
Yeast
Superoxide Dismutase
Zinc
Copper
Yeasts
Post Translational Protein Processing
Enzymes
Disulfides
Cytosol
Cysteine
Assays
Proteins
Peptides
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria. / Field, Lori Sturtz; Furukawa, Yoshiaki; O'Halloran, Thomas V.; Culotta, Valeria Cizewski.

In: Journal of Biological Chemistry, Vol. 278, No. 30, 25.07.2003, p. 28052-28059.

Research output: Contribution to journalArticle

Field, Lori Sturtz ; Furukawa, Yoshiaki ; O'Halloran, Thomas V. ; Culotta, Valeria Cizewski. / Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 30. pp. 28052-28059.
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