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Article: Essential Regulation of Cell Bioenergetics by Constitutive InsP 3 Receptor Ca 2+ Transfer to Mitochondria

TitleEssential Regulation of Cell Bioenergetics by Constitutive InsP 3 Receptor Ca 2+ Transfer to Mitochondria
Authors
KeywordsCellbio
Signaling
Issue Date2010
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2010, v. 142 n. 2, p. 270-283 How to Cite?
AbstractMechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP 3R-mediated Ca 2+ release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP 3R Ca 2+ signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca 2+ uptake. Mitochondrial uptake of InsP 3R-released Ca 2+ is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca 2+ transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsP 3R Ca 2+ release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics. © 2010 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/132532
ISSN
2015 Impact Factor: 28.71
2015 SCImago Journal Rankings: 28.188
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHGM/DK56328
MH059937
DK075048
CA099179
CA092660
GM48071
GM065830
American Heart Association
DK079572
Funding Information:

We thank Dr. Robert Balaban for helpful discussions. This work was supported by NIH grants GM/DK56328 and MH059937 (J.K.F.), DK075048 (K. R. H.), CA099179 and CA092660 (C. T.), GM48071 (I. P.), and GM065830 (J.K.F. and I. P.). We thank the University of Pennsylvania Institute for Diabetes, Obesity and Metabolism (P30-DK19535) for assistance. C. C. was supported by an award from the American Heart Association. R. A. M. was supported by DK079572.

References

 

DC FieldValueLanguage
dc.contributor.authorCárdenas, Cen_HK
dc.contributor.authorMiller, RAen_HK
dc.contributor.authorSmith, Ien_HK
dc.contributor.authorBui, Ten_HK
dc.contributor.authorMolgó, Jen_HK
dc.contributor.authorMüller, Men_HK
dc.contributor.authorVais, Hen_HK
dc.contributor.authorCheung, KHen_HK
dc.contributor.authorYang, Jen_HK
dc.contributor.authorParker, Ien_HK
dc.contributor.authorThompson, CBen_HK
dc.contributor.authorBirnbaum, MJen_HK
dc.contributor.authorHallows, KRen_HK
dc.contributor.authorFoskett, JKen_HK
dc.date.accessioned2011-03-28T09:26:01Z-
dc.date.available2011-03-28T09:26:01Z-
dc.date.issued2010en_HK
dc.identifier.citationCell, 2010, v. 142 n. 2, p. 270-283en_HK
dc.identifier.issn0092-8674en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132532-
dc.description.abstractMechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP 3R-mediated Ca 2+ release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP 3R Ca 2+ signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca 2+ uptake. Mitochondrial uptake of InsP 3R-released Ca 2+ is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca 2+ transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsP 3R Ca 2+ release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics. © 2010 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellen_HK
dc.relation.ispartofCellen_HK
dc.subjectCellbioen_HK
dc.subjectSignalingen_HK
dc.titleEssential Regulation of Cell Bioenergetics by Constitutive InsP 3 Receptor Ca 2+ Transfer to Mitochondriaen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, KH: kingho.cheung@hku.hken_HK
dc.identifier.authorityCheung, KH=rp01463en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.cell.2010.06.007en_HK
dc.identifier.pmid20655468-
dc.identifier.pmcidPMC2911450-
dc.identifier.scopuseid_2-s2.0-77955041880en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955041880&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume142en_HK
dc.identifier.issue2en_HK
dc.identifier.spage270en_HK
dc.identifier.epage283en_HK
dc.identifier.isiWOS:000280204300018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10004794956-
dc.identifier.scopusauthoridCárdenas, C=7003841618en_HK
dc.identifier.scopusauthoridMiller, RA=36188494400en_HK
dc.identifier.scopusauthoridSmith, I=7404425960en_HK
dc.identifier.scopusauthoridBui, T=13907874300en_HK
dc.identifier.scopusauthoridMolgó, J=7006666682en_HK
dc.identifier.scopusauthoridMüller, M=7404689330en_HK
dc.identifier.scopusauthoridVais, H=6602154738en_HK
dc.identifier.scopusauthoridCheung, KH=14007487800en_HK
dc.identifier.scopusauthoridYang, J=9239264300en_HK
dc.identifier.scopusauthoridParker, I=35550719600en_HK
dc.identifier.scopusauthoridThompson, CB=35373390800en_HK
dc.identifier.scopusauthoridBirnbaum, MJ=35430895100en_HK
dc.identifier.scopusauthoridHallows, KR=6603441310en_HK
dc.identifier.scopusauthoridFoskett, JK=7005723620en_HK
dc.identifier.citeulike7586698-

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