Mitochondrial Ca(2+) and apoptosis - PubMed (original) (raw)

Review

doi: 10.1016/j.ceca.2012.02.008. Epub 2012 Apr 3.

Federica Baldassari, Angela Bononi, Massimo Bonora, Elena De Marchi, Saverio Marchi, Sonia Missiroli, Simone Patergnani, Alessandro Rimessi, Jan M Suski, Mariusz R Wieckowski, Paolo Pinton

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Review

Mitochondrial Ca(2+) and apoptosis

Carlotta Giorgi et al. Cell Calcium. 2012 Jul.

Abstract

Mitochondria are key decoding stations of the apoptotic process. In support of this view, a large body of experimental evidence has unambiguously revealed that, in addition to the well-established function of producing most of the cellular ATP, mitochondria play a fundamental role in triggering apoptotic cell death. Various apoptotic stimuli cause the release of specific mitochondrial pro-apoptotic factors into the cytosol. The molecular mechanism of this release is still controversial, but there is no doubt that mitochondrial calcium (Ca(2+)) overload is one of the pro-apoptotic ways to induce the swelling of mitochondria, with perturbation or rupture of the outer membrane, and in turn the release of mitochondrial apoptotic factors into the cytosol. Here, we review as different proteins that participate in mitochondrial Ca(2+) homeostasis and in turn modulate the effectiveness of Ca(2+)-dependent apoptotic stimuli. Strikingly, the final outcome at the cellular level is similar, albeit through completely different molecular mechanisms: a reduced mitochondrial Ca(2+) overload upon pro-apoptotic stimuli that dramatically blunts the apoptotic response.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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Figures

Fig. 1

Fig. 1

Schematic intracellular distribution of the reported proteins involved in ER–mitochondria Ca2+ cross-talk. Abbreviations: AKT, v-akt murine thymoma viral oncogene homologue; BAX, Bcl-2-associated X; Bcl-xL, B-cell lymphomas extra long; Bcl-2, B-cell lymphomas 2; BIK, Bcl-2 interacting killer; ER, endoplasmic reticulum; FHIT, fragile histidine triad; grp75, glucose-regulated protein 75; IP3R, inositol 1,4,5-trisphosphate receptor; MAMs, mitochondria-associated membranes; mcl-1, myeloid cell leukaemia-1; MFN-1/-2, mitofusin-1, -2; p66Shc, 66-kDa isoform of the growth factor adapter shc; PML, promyelocytic leukaemia protein; PP2a, protein phosphatase 2a; SERCA, sarco-endoplasmic reticulum Ca2+ ATPase; Sig-1R, Sigma-1 receptor; STAT, Signal Transducer and Activator of Transcription; VDAC, voltage-dependent anion channel.

Fig. 2

Fig. 2

Schematic representation of mitochondrial Ca2+-dependent apoptosis.

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