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Essential Regulation of Cell Bioenergetics by Constitutive InsP(3) Receptor Ca(2+) Transfer to Mitochondria.

Identifieur interne : 00AB06 ( Main/Merge ); précédent : 00AB05; suivant : 00AB07

Essential Regulation of Cell Bioenergetics by Constitutive InsP(3) Receptor Ca(2+) Transfer to Mitochondria.

Auteurs : César Cárdenas [États-Unis] ; Russell A. Miller [États-Unis] ; Ian Smith [États-Unis] ; Thi Bui [États-Unis] ; Jordi Molg [France] ; Marioly Müller [États-Unis] ; Horia Vais [États-Unis] ; King-Ho Cheung [États-Unis] ; Jun Yang [États-Unis] ; Ian Parker [États-Unis] ; Craig B. Thompson [États-Unis] ; Morris J. Birnbaum [États-Unis] ; Kenneth R. Hallows [États-Unis] ; J Kevin Foskett [États-Unis]

Source :

Cell [ 0092-8674 ] ; 2010-07-23.

RBID : Hal:hal-00506136

Abstract

Mechanisms 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(3)R-mediated Ca(2+) release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP(3)R 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(3)R-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(3)R Ca(2+) release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.

Url:

https://hal.archives-ouvertes.fr/hal-00506136

DOI: 10.1016/j.cell.2010.06.007

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<author><name sortKey="Muller, Marioly" sort="Muller, Marioly" uniqKey="Muller M" first="Marioly" last="Müller">Marioly Müller</name>
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<author><name sortKey="Vais, Horia" sort="Vais, Horia" uniqKey="Vais H" first="Horia" last="Vais">Horia Vais</name>
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<author><name sortKey="Cheung, King Ho" sort="Cheung, King Ho" uniqKey="Cheung K" first="King-Ho" last="Cheung">King-Ho Cheung</name>
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<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
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</author>
<author><name sortKey="Foskett, J Kevin" sort="Foskett, J Kevin" uniqKey="Foskett J" first="J Kevin" last="Foskett">J Kevin Foskett</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-122378" status="INCOMING">          <orgName>Department of Physiology, University of Pennsylvania</orgName>
          <desc>            <address>              <addrLine>Philadelphia, PA 19104</addrLine>
              <country key="US"></country>
            </address>
          </desc>
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</analytic>
<idno type="DOI">10.1016/j.cell.2010.06.007</idno>
<series><title level="j">Cell</title>
<idno type="ISSN">0092-8674</idno>
<imprint><date type="datePub">2010-07-23</date>
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<front><div type="abstract" xml:lang="en">Mechanisms 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(3)R-mediated Ca(2+) release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP(3)R 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(3)R-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(3)R Ca(2+) release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.</div>
</front>
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Essential Regulation of Cell Bioenergetics by Constitutive InsP(3) Receptor Ca(2+) Transfer to Mitochondria.

Essential Regulation of Cell Bioenergetics by Constitutive InsP(3) Receptor Ca(2+) Transfer to Mitochondria.

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