Bax and heart mitochondria: uncoupling and inhibition of respiration without permeability transition

Appaix, Florence; Guerrero, Karen; Rampal, David; Izikki, Mohamed; Käämbre, Tuuli; Sikk, Peeter; Brdiczka, Dieter; Riva-Lavieille, Catherine; Olivares, José; Longuet, Michel; Antonsson, Bruno; Saks, Valdur

doi:10.1016/s0005-2728(02)00358-4

Cited by 25 publications

(16 citation statements)

References 43 publications

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“… MCU, electrogenic mitochondrial Ca 2+ uniporter; mNCX, mitochondrial Na + /Ca 2+ exchanger; NHE, Na + /H + exchanger; nSR, network SR; PTP, permeability transition pore; “?” – questionable 1 , Akar et al, 2005 2 , Altschafl et al, 2007 3 , Appaix et al, 2002 4 , Arnaudeau et al, 2001 5 , Ban et al, 1999 6 , Bandyopadhyay et al, 2000 7 , Brandes et al, 2002 8 , Budd et al, 1996 9 , Budd and Nicholls, 1996 10 , Cox et al, 1993 11 , Gincel et al, 2001 12 , Jordani et. al., 2000…”

Section: Figurementioning

confidence: 99%

Mitochondria in cardiomyocyte Ca2+ signaling

Lukyanenko

Chikando

Lederer

2009

The International Journal of Biochemistry & Cell Biology

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Ca2+ signaling is of vital importance to cardiac cell function and plays an important role in heart failure. It is based on sarcolemmal, sarcoplasmic reticulum and mitochondrial Ca2+ cyclings. While the first two are well characterized, the latter remains unclear, controversial and technically challenging. In mammalian cardiac myocytes, Ca2+ influx through L-type calcium channels in the sarcolemmal membrane triggers Ca2+ release from the nearby junctional sarcoplasmic reticulum to produce Ca2+ sparks. When this triggering is synchronized by the cardiac action potential, a global [Ca2+]i transient arises from the coordinated Ca2+ release events. The ends of intermyofibrillar mitochondria are located within 20 nm of the junctional sarcoplasmic reticulum and thereby experience the high local [Ca2+] during the Ca2+ release process. Both local and global Ca2+ signals may thus influence calcium signaling in mitochondria and, reciprocally, mitochondria may contribute to local control of calcium signaling. In addition to the intermyofibrillar mitochondria, morphologically distinct mitochondria are also located in the perinuclear and subsarcolemmal regions of the cardiomyocyte and thus experience different local [Ca2+]. Here we review the literature in regard to several issues of broad interest: (1) the ultrastructural basis for mitochondrion - sarcoplasmic reticulum cross-signaling; (2) mechanisms of sarcoplasmic reticulum signaling; (3) mitochondrial calcium signaling; and (4) the possible interplay of calcium signaling between the sarcoplasmic reticulum and adjacent mitochondria. Finally, this review discusses experimental findings and mathematical models of cardiac calcium signaling between the sarcoplasmic reticulum and mitochondria, identifies weaknesses in these models, and suggests strategies and approaches for future investigations.

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Section: Figurementioning

confidence: 99%

Mitochondria in cardiomyocyte Ca2+ signaling

Lukyanenko

Chikando

Lederer

2009

The International Journal of Biochemistry & Cell Biology

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“…In the presence of Mg which inhibits MPT, however, Bax led to mild proton leak and cytochrome c release via formation of pores in the OM, independent of MPT [1]. Later it was shown that Bax, Bak and cardiolipin can form a megachannel (<2 MB) in the OM to release cytochrome c and other proapoptotic molecules sequestered in the intermembrane space [45].…”

Section: Role Of Mpt In Ischemia/reperfusion (Ir) Injurymentioning

confidence: 99%

Mitochondrial Permeability Transition in Cardiac Cell Injury and Death

Honda

Ping

2006

Cardiovasc Drugs Ther

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Mitochondria can serve as the arbiter of cell fate in response to stress. Mitochondrial permeability transition (MPT) is characterized by permeabilization of an otherwise relatively impermeable mitochondrial inner membrane and appears to have a major role in ischemia/reperfusion (I/R) injury in myocardial infarction and stroke. After I/R, the fate of the cell is determined by the extent of MPT. If minimal, the cell may recover; if moderate, the cell may undergo programmed cell death; if severe, the cell may die from necrosis due to inadequate energy production. After reviewing the role of MPT in disease, we examine the signaling and metabolic networks that regulate MPT. We then conclude with some of the challenges in future MPT research.

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“…Release by 2-APB-Release of the mitochondrial intermembrane protein cytochrome c typically accompanies the osmotic swelling and rupture of the outer membrane evoked by activation of the PTP (45)(46)(47). Loss of mitochondrial matrix pyridine nucleotides is another measure of the PTP, distinguishing it from a mechanism of depolarization mediated by activation of a "low conductance" pore (48).…”

Section: Inhibition Of Ca 2ϩ -Induced Mitochondrial Cytochrome C and mentioning

confidence: 99%

Cyclosporin A-insensitive Permeability Transition in Brain Mitochondria

Chinopoulos

Starkov

Fiskum

2003

Journal of Biological Chemistry

123

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The mitochondrial permeability transition pore (PTP) may operate as a physiological Ca 2؉ release mechanism and also contribute to mitochondrial deenergization and release of proapoptotic proteins after pathological stress, e.g. ischemia/reperfusion. Brain mitochondria exhibit unique PTP characteristics, including relative resistance to inhibition by cyclosporin A. In this study, we report that 2-aminoethoxydiphenyl borate blocks Ca 2؉ -induced Ca 2؉ release in isolated, non-synaptosomal rat brain mitochondria in the presence of physiological concentrations of ATP and Mg 2؉ . Ca 2؉ release was not mediated by the mitochondrial Na ؉ /Ca 2؉ exchanger or by reversal of the uniporter responsible for energy-dependent Ca 2؉ uptake. Loss of mitochondrial Ca 2؉ was accompanied by release of cytochrome c and pyridine nucleotides, indicating an increase in permeability of both the inner and outer mitochondrial membranes. Under these conditions, Ca 2؉ -induced opening of the PTP was not blocked by cyclosporin A, antioxidants, or inhibitors of phospholipase A 2 or nitric-oxide synthase but was abolished by pretreatment with bongkrekic acid. These findings indicate that in the presence of adenine nucleotides and Mg 2؉ , Ca 2؉ -induced PTP in non-synaptosomal brain mitochondria exhibits a unique pattern of sensitivity to inhibitors and is particularly responsive to 2-aminoethoxydiphenyl borate.Mitochondria are temporo-spatial modulators of cytosolic [Ca 2ϩ ] through their ability to both sequester and release Ca 2ϩ in concert with Ca 2ϩ transport across the endoplasmic reticulum (1, 2). Physiological mitochondrial Ca 2ϩ efflux, including that caused by Ca 2ϩ -induced Ca 2ϩ release (mCICR), 1 is attributed to either activation of the permeability transition pore (PTP) (3, 4) or to reversal of the Ca 2ϩ uniporter (5). Opening of the PTP has been implicated as a mediator of apoptotic and necrotic cell death as well as a regulator of normal cell Ca 2ϩ homeostasis (4, 6 -12). The characteristic traits of the PTP include reversibility (13), sensitivity to inhibition by cyclosporin A (14), and mitochondrial swelling associated with loss of matrix solutes (15-17). Cyclosporin A is not always effective, however, at inhibiting Ca 2ϩ -induced mitochondrial swelling and loss of ⌬⌿ (18 -22). In addition, the observation that normal intracellular concentrations of adenine nucleotides and Mg 2ϩ partially or completely block PTP activation (23, 24) casts doubt on a physiological role of the PTP.The extent to which mitochondria swell in response to accumulation of large Ca 2ϩ loads also varies considerably with experimental conditions and with mitochondrial tissue type (25-27). Brain mitochondria are particularly resistant to Ca 2ϩ -induced swelling (25, 28); moreover, they represent many cell populations, which may explain their heterogeneous response to large Ca 2ϩ loads and to inhibitors of the PTP, e.g. cyclosporin A (26,29).In this study we report that 2-APB (30) prevents Ca 2ϩ -induced PTP in non-synaptosomal brain mitochondria in the ...

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Bax and heart mitochondria: uncoupling and inhibition of respiration without permeability transition

Cited by 25 publications

References 43 publications

Mitochondria in cardiomyocyte Ca2+ signaling

Mitochondria in cardiomyocyte Ca2+ signaling

Mitochondrial Permeability Transition in Cardiac Cell Injury and Death

Cyclosporin A-insensitive Permeability Transition in Brain Mitochondria

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