Linked Life Data

12748182

Source:http://linkedlifedata.com/resource/pubmed/id/12748182

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2003-7-21
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28052-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria.
pubmed:affiliation
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't