Matches in SemOpenAlex for { <https://semopenalex.org/work/W2331915496> ?p ?o ?g. }
Showing items 1 to 77 of
77
with 100 items per page.
- W2331915496 endingPage "570a" @default.
- W2331915496 startingPage "570a" @default.
- W2331915496 abstract "Mitochondrial Ca2+ is regulated by Ca2+ transport proteins in the mitochondrial inner membrane. Among these are the mitochondrial calcium uniporter (MCU), a Ca2+ channel responsible for most Ca2+ uptake in mitochondria, and NCLX, a Na+/Ca2+ exchanger, mediating Ca2+ release to the cytosol. After more than five decades of intensive study, the MCU gene was finally cloned in 2010. Strikingly, MCU-KO mouse, whose mitochondria lose >90% Ca2+ uptake capacity, was born normally with very mild phenotype and only slight reduction of mitochondrial Ca2+. How does the animal maintain normal physiology without MCU, which is highly conserved and tightly regulated in most eukaryotes?To address this issue, we use an MCU-KO HEK293T line as our model system. Consistent with animal experiments, these cells have normal mitochondrial morphology, matrix [Ca2+], and ATP production via oxidative phosphorylation. Interestingly, we observed a slow Ca2+ uptake in MCU-KO mitochondria, operating at 5-10% of the MCU capacity, resistant to a potent MCU inhibitor Ru360. Furthermore, these mitochondria lose Na+-dependent Ca2+ release, due to decreased expression of the NCLX protein. We therefore propose that mitochondria compensate the loss of MCU by invoking a backup Ca2+ uptake mechanism, and by suppressing Ca2+ release. Supporting this hypothesis, we show that expressing NCLX in MCU-free mitochondria drastically reduces matrix [Ca2+], and abolishes >80% ATP output. Moreover, overexpression of WT-NCLX, but not a loss-of-function mutant S468A-NCLX, induces rapid death of MCU-KO cells.We’re now investigating how mitochondria invoke these compensatory mechanisms. Na+/Ca2+ exchange can be restored by introducing human MCU gene into MCU-KO cells, but not by expressing transport-capable MCU homologues from A. thaliana or D. Discoideum, implicating that mitochondria might balance Ca2+ uptake and release through an MCU-NCLX interaction that stabilizes inner-membrane expression of NCLX." @default.
- W2331915496 created "2016-06-24" @default.
- W2331915496 creator A5008760207 @default.
- W2331915496 creator A5041877785 @default.
- W2331915496 creator A5044653429 @default.
- W2331915496 date "2015-01-01" @default.
- W2331915496 modified "2023-09-26" @default.
- W2331915496 title "Mitochondrial Calcium and Bioenergetics Controlled by Tight Coordination of MCU and NCLX" @default.
- W2331915496 doi "https://doi.org/10.1016/j.bpj.2014.11.3119" @default.
- W2331915496 hasPublicationYear "2015" @default.
- W2331915496 type Work @default.
- W2331915496 sameAs 2331915496 @default.
- W2331915496 citedByCount "0" @default.
- W2331915496 crossrefType "journal-article" @default.
- W2331915496 hasAuthorship W2331915496A5008760207 @default.
- W2331915496 hasAuthorship W2331915496A5041877785 @default.
- W2331915496 hasAuthorship W2331915496A5044653429 @default.
- W2331915496 hasBestOaLocation W23319154961 @default.
- W2331915496 hasConcept C100206155 @default.
- W2331915496 hasConcept C11701378 @default.
- W2331915496 hasConcept C12554922 @default.
- W2331915496 hasConcept C178790620 @default.
- W2331915496 hasConcept C181199279 @default.
- W2331915496 hasConcept C185592680 @default.
- W2331915496 hasConcept C28859421 @default.
- W2331915496 hasConcept C35341161 @default.
- W2331915496 hasConcept C519063684 @default.
- W2331915496 hasConcept C55493867 @default.
- W2331915496 hasConcept C57600042 @default.
- W2331915496 hasConcept C86803240 @default.
- W2331915496 hasConcept C95444343 @default.
- W2331915496 hasConcept C98539663 @default.
- W2331915496 hasConceptScore W2331915496C100206155 @default.
- W2331915496 hasConceptScore W2331915496C11701378 @default.
- W2331915496 hasConceptScore W2331915496C12554922 @default.
- W2331915496 hasConceptScore W2331915496C178790620 @default.
- W2331915496 hasConceptScore W2331915496C181199279 @default.
- W2331915496 hasConceptScore W2331915496C185592680 @default.
- W2331915496 hasConceptScore W2331915496C28859421 @default.
- W2331915496 hasConceptScore W2331915496C35341161 @default.
- W2331915496 hasConceptScore W2331915496C519063684 @default.
- W2331915496 hasConceptScore W2331915496C55493867 @default.
- W2331915496 hasConceptScore W2331915496C57600042 @default.
- W2331915496 hasConceptScore W2331915496C86803240 @default.
- W2331915496 hasConceptScore W2331915496C95444343 @default.
- W2331915496 hasConceptScore W2331915496C98539663 @default.
- W2331915496 hasIssue "2" @default.
- W2331915496 hasLocation W23319154961 @default.
- W2331915496 hasOpenAccess W2331915496 @default.
- W2331915496 hasPrimaryLocation W23319154961 @default.
- W2331915496 hasRelatedWork W1067830394 @default.
- W2331915496 hasRelatedWork W1779480319 @default.
- W2331915496 hasRelatedWork W1969575699 @default.
- W2331915496 hasRelatedWork W1987868452 @default.
- W2331915496 hasRelatedWork W2010932100 @default.
- W2331915496 hasRelatedWork W2065569764 @default.
- W2331915496 hasRelatedWork W2094254313 @default.
- W2331915496 hasRelatedWork W2094863984 @default.
- W2331915496 hasRelatedWork W2124273972 @default.
- W2331915496 hasRelatedWork W2781569872 @default.
- W2331915496 hasRelatedWork W2794942839 @default.
- W2331915496 hasRelatedWork W2905643675 @default.
- W2331915496 hasRelatedWork W3014109758 @default.
- W2331915496 hasRelatedWork W3024671728 @default.
- W2331915496 hasRelatedWork W3041353228 @default.
- W2331915496 hasRelatedWork W3099592172 @default.
- W2331915496 hasRelatedWork W3149656605 @default.
- W2331915496 hasRelatedWork W317702839 @default.
- W2331915496 hasRelatedWork W3198444904 @default.
- W2331915496 hasRelatedWork W2183275921 @default.
- W2331915496 hasVolume "108" @default.
- W2331915496 isParatext "false" @default.
- W2331915496 isRetracted "false" @default.
- W2331915496 magId "2331915496" @default.
- W2331915496 workType "article" @default.