Matches in SemOpenAlex for { <https://semopenalex.org/work/W2220105963> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W2220105963 abstract "The stress response to exogenous H2O2 has provided significant insight into thiol-based cytosolic H2O2 sensors such as OxyR in Escherichia coli and its eukaryotic counterpart Gpx3/Yap1 in Saccharomyce cerevisiae. However, sensing of endogenously generated H2O2 in mitochondria, the main sites of H2O2 production in respiring yeast, is poorly documented. We have recently demonstrated that cytochrome c peroxidase (Ccp1) acts as a mitochondrial H2O2 sensor to balance reactive oxygen species (ROS) levels by regulating catalase A (Cta1) activity and attenuating the H2O2 stress response during aging. Since Ccp1 is the first heme-based H2O2 sensor to be identified, its mechanism of action at the molecular level is of much interest. This thesis reports on how H2O2 signals through Ccp1. Activity assays reveal the accumulation of catalytically inactive and heme-free Ccp1 outside mitochondria in respiring cells, when catalase activity starts to increase. Importantly, the burst in H2O2 generation during the switch from fermentation to respiration triggers heme-mediated oxidation by H2O2 of the proximal Fe ligand, H175. Formation of oxo-H175 weakens the heme-ligand interaction and labilizes the heme group, which is transferred either directly or via unidentified intermediate(s) to apoCta1. The nascent Cta1 activity detoxifies H2O2, and apoCcp1 which has conformational lability, undergoes reverse translocation to the vacuole and nucleus. Mass spectrometric characterization of heme-mediated H2O2-induced chemical and post-translational modifications in recombinant Ccp1 and Ccp1 isolated from yeast cells, respectively, has allowed us to identify the residues oxidized as well as to evaluate radical-transfer pathways in Ccp1 in response to both exogenous and endogenous H2O2. Importantly, the mass spectrometry-based approach described here provides a way to fully evaluate the oxidation profile of a protein. Although Cta1 was not found as a binding partner of GST-Ccp1 in GST pull-down assays, the antioxidant proteins, manganese superoxide dismutase (Sod2), thioredoxin peroxidase (Tsa1), the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the putative heme transporter Pet9 and heat shock proteins 70 and 90 were reproducibly found as Ccp1 binding partners. Combined, the results presented provide insights into the mechanism of H2O2 signaling in cells involving heme-mediated redox changes in contrast to the redox chemistry of thiols." @default.
- W2220105963 created "2016-06-24" @default.
- W2220105963 creator A5055853806 @default.
- W2220105963 date "2015-09-17" @default.
- W2220105963 modified "2023-09-27" @default.
- W2220105963 title "Biochemical and mass spectrometric analysis of yeast cytochrome c peroxidase in vitro and in vivo gives insights into its biological functions as a H2O2 sensor and heme donor protein" @default.
- W2220105963 hasPublicationYear "2015" @default.
- W2220105963 type Work @default.
- W2220105963 sameAs 2220105963 @default.
- W2220105963 citedByCount "0" @default.
- W2220105963 crossrefType "dissertation" @default.
- W2220105963 hasAuthorship W2220105963A5055853806 @default.
- W2220105963 hasConcept C12554922 @default.
- W2220105963 hasConcept C133166286 @default.
- W2220105963 hasConcept C162008176 @default.
- W2220105963 hasConcept C181199279 @default.
- W2220105963 hasConcept C185592680 @default.
- W2220105963 hasConcept C20705724 @default.
- W2220105963 hasConcept C2776151105 @default.
- W2220105963 hasConcept C2776217839 @default.
- W2220105963 hasConcept C2777576037 @default.
- W2220105963 hasConcept C2778979269 @default.
- W2220105963 hasConcept C2779222958 @default.
- W2220105963 hasConcept C28859421 @default.
- W2220105963 hasConcept C29311851 @default.
- W2220105963 hasConcept C48349386 @default.
- W2220105963 hasConcept C55493867 @default.
- W2220105963 hasConcept C86803240 @default.
- W2220105963 hasConcept C95444343 @default.
- W2220105963 hasConcept C98539663 @default.
- W2220105963 hasConceptScore W2220105963C12554922 @default.
- W2220105963 hasConceptScore W2220105963C133166286 @default.
- W2220105963 hasConceptScore W2220105963C162008176 @default.
- W2220105963 hasConceptScore W2220105963C181199279 @default.
- W2220105963 hasConceptScore W2220105963C185592680 @default.
- W2220105963 hasConceptScore W2220105963C20705724 @default.
- W2220105963 hasConceptScore W2220105963C2776151105 @default.
- W2220105963 hasConceptScore W2220105963C2776217839 @default.
- W2220105963 hasConceptScore W2220105963C2777576037 @default.
- W2220105963 hasConceptScore W2220105963C2778979269 @default.
- W2220105963 hasConceptScore W2220105963C2779222958 @default.
- W2220105963 hasConceptScore W2220105963C28859421 @default.
- W2220105963 hasConceptScore W2220105963C29311851 @default.
- W2220105963 hasConceptScore W2220105963C48349386 @default.
- W2220105963 hasConceptScore W2220105963C55493867 @default.
- W2220105963 hasConceptScore W2220105963C86803240 @default.
- W2220105963 hasConceptScore W2220105963C95444343 @default.
- W2220105963 hasConceptScore W2220105963C98539663 @default.
- W2220105963 hasLocation W22201059631 @default.
- W2220105963 hasOpenAccess W2220105963 @default.
- W2220105963 hasPrimaryLocation W22201059631 @default.
- W2220105963 hasRelatedWork W1986049211 @default.
- W2220105963 hasRelatedWork W2027320785 @default.
- W2220105963 hasRelatedWork W2029877800 @default.
- W2220105963 hasRelatedWork W2057315471 @default.
- W2220105963 hasRelatedWork W2066351331 @default.
- W2220105963 hasRelatedWork W2070498825 @default.
- W2220105963 hasRelatedWork W2090782332 @default.
- W2220105963 hasRelatedWork W2093447227 @default.
- W2220105963 hasRelatedWork W2093528624 @default.
- W2220105963 hasRelatedWork W2111859500 @default.
- W2220105963 hasRelatedWork W2223889910 @default.
- W2220105963 hasRelatedWork W2501641743 @default.
- W2220105963 hasRelatedWork W2883577714 @default.
- W2220105963 hasRelatedWork W2888340233 @default.
- W2220105963 hasRelatedWork W2895791964 @default.
- W2220105963 hasRelatedWork W2905217852 @default.
- W2220105963 hasRelatedWork W2956120259 @default.
- W2220105963 hasRelatedWork W3083946638 @default.
- W2220105963 hasRelatedWork W3198656270 @default.
- W2220105963 hasRelatedWork W89273739 @default.
- W2220105963 isParatext "false" @default.
- W2220105963 isRetracted "false" @default.
- W2220105963 magId "2220105963" @default.
- W2220105963 workType "dissertation" @default.