Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis

Leist, Marcel; Single, Barbara; Castoldi, Anna Federica; Kühnle, Simone; Nicotera, Pierluigi

doi:10.1084/jem.185.8.1481

Cited by 1,745 publications

(1,297 citation statements)

References 24 publications

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“…An interesting possibility is that release of cytochrome c in hair cells may be a common early step that triggers cell death processing. Several factors are known to contribute to the particular cell death pathway selected; these include the level of caspases activated, the energy available in the form of ATP (Leist et al 1997), and the nature and severity of the insult (Bonfoco et al 1995).…”

Section: Discussionmentioning

confidence: 99%

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nicotera

Henderson

2003

JARO - Journal of the Association for Research in Otolaryngolog

168

155

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We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.

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Section: Discussionmentioning

confidence: 99%

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nicotera

Henderson

2003

JARO - Journal of the Association for Research in Otolaryngolog

168

155

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“…Upon T cell activation, cell death preferentially occurred via necrosis rather than apoptosis in patients with SLE. ATP levels and ATP/ADP ratios were profoundly diminished in lupus PBL, which accounts for predisposition to necrosis [64].…”

Section: Mitochondrial Hyperpolarization and Increased No Production mentioning

confidence: 99%

Nitric oxide, mitochondrial hyperpolarization, and T cell activation☆

Nagy

Koncz

Fernández

et al. 2007

Free Radical Biology and Medicine

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T lymphocyte activation is associated with nitric oxide (NO) production that plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both T lymphocyte activation and apoptosis, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus (SLE) induces mitochondrial biogenesis and alters Ca 2+ signaling. Thus, while NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity.

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“…10 Necrosis is likely to result, at least in part, from severe ATP depletion. 11 Such cell death pathways can be divided into distinct stages ( Figure 1). During the initial signaling stage, cells integrate metabolic stress signals, sense DNA damage, or receive critical information from the extracellular space or from neighboring cells, often through specific cell surface receptors.…”

Section: Cell Death Types Mechanisms and Stagesmentioning

confidence: 99%

Redundant cell death mechanisms as relics and backups

Golstein

Kroemer

2005

Cell Death Differ

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Here we review recent observations indicating the existence of redundant cell death mechanisms. We speculate that this redundancy reflects a particular evolutionary history for cellular demise. Autophagic or apoptotic elements might have been added to a primordial death mechanism, initially improving cell dismantling and later acquiring the ability to act themselves as death effectors. The resulting redundancy of cell death mechanisms has pathophysiological implications.

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Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis

Cited by 1,745 publications

References 24 publications

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nitric oxide, mitochondrial hyperpolarization, and T cell activation☆

Redundant cell death mechanisms as relics and backups

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