Linked Life Data

20798245

Source:http://linkedlifedata.com/resource/pubmed/id/20798245

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-2
pubmed:abstractText
PKC? has emerged as a novel regulatory molecule of oxidative phosphorylation by targeting the pyruvate dehydrogenase complex (PDHC). We showed that activation of PKC? leads to the dephosphorylation of pyruvate dehydrogenase kinase 2 (PDK2), thereby decreasing PDK2 activity and increasing PDH activity, accelerating oxygen consumption, and augmenting ATP synthesis. However, the molecular components that mediate PKC? signaling in mitochondria have remained elusive so far. Here, we identify for the first time a functional complex, which includes cytochrome c as the upstream driver of PKC?, and uses the adapter protein p66Shc as a platform with vitamin A (retinol) as a fourth partner. All four components are necessary for the activation of the PKC? signal chain. Genetic ablation of any one of the three proteins, or retinol depletion, silences signaling. Furthermore, mutations that disrupt the interaction of cytochrome c with p66Shc, of p66Shc with PKC?, or the deletion of the retinol-binding pocket on PKC?, attenuate signaling. In cytochrome c-deficient cells, reintroduction of cytochrome c Fe(3+) protein restores PKC? signaling. Taken together, these results indicate that oxidation of PKC? is key to the activation of the pathway. The PKC?/p66Shc/cytochrome c signalosome might have evolved to effect site-directed oxidation of zinc-finger structures of PKC?, which harbor the activation centers and the vitamin A binding sites. Our findings define the molecular mechanisms underlying the signaling function of PKC? in mitochondria.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5033-42
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Regulation of intermediary metabolism by the PKCdelta signalosome in mitochondria.
pubmed:affiliation
Department of Neurology and Neurobiology, Weill-Cornell Medical School, New York, New York, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural