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Journal ArticleDOI

Mitochondria and cell death: outer membrane permeabilization and beyond

TLDR
MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences.
Abstract
Mitochondrial outer membrane permeabilization (MOMP) is often required for activation of the caspase proteases that cause apoptotic cell death. Various intermembrane space (IMS) proteins, such as cytochrome c, promote caspase activation following their mitochondrial release. As a consequence, mitochondrial outer membrane integrity is highly controlled, primarily through interactions between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein family. Following MOMP by pro-apoptotic BCL-2-associated X protein (BAX) or BCL-2 antagonist or killer (BAK), additional regulatory mechanisms govern the mitochondrial release of IMS proteins and caspase activity. MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences.

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Journal ArticleDOI

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Lorenzo Galluzzi, +186 more
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Journal ArticleDOI

The unfolded protein response: controlling cell fate decisions under ER stress and beyond

TL;DR: Insight is provided into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6).
Journal ArticleDOI

Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

TL;DR: The biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold are discussed, illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCA2 protein family.
Journal ArticleDOI

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

TL;DR: A functional classification of cell death subroutines is proposed that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic programmed cell death, regulated necrosis, autophagic cell death and mitotic catastrophe.
Journal ArticleDOI

Activation of Apoptosis Signalling Pathways by Reactive Oxygen Species

TL;DR: ROS play a central role in cell signalling as well as in regulation of the main pathways of apoptosis mediated by mitochondria, death receptors and the endoplasmic reticulum, and current understanding of the role of ROS in each of these three main pathways is focused on.
References
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Journal ArticleDOI

Resistance to caspase-independent cell death requires persistence of intact mitochondria

TL;DR: iMOMP provides a critical source of intact mitochondria that permits cellular survival following MOMP, suggesting that the resistance of these mitochondria to MOMp lies at the point of Bax or Bak activation.
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The BH3-only Bnip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms

TL;DR: The results uncover a direct link between Opa1 on the inner mitochondrial membrane and the apoptotic machinery on the outer membrane that modulates fusion and cristae structure by separate mechanisms, which might help to unravel optic atrophy aetiology.
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Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2.

TL;DR: It is concluded that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.
Journal ArticleDOI

Real-time single cell analysis of Smac/DIABLO release during apoptosis

TL;DR: There was no significant difference in the time to the onset of release, and both cyt-c-GFP and Smac/DIABLO-YFP release coincided with mitochondrial membrane potential depolarization, and there were no significant differences when z-VAD-fmk–sensitive caspases were inhibited or Casp-3 was reintroduced.
Journal ArticleDOI

A non-apoptotic role for caspase-9 in muscle differentiation.

TL;DR: Caspase-9, an initiator caspase in the mitochondrial death pathway, is responsible for the activation of caspases-3 in differentiating C2C12 cells, suggesting that the mitochondrial pathway is required for differentiation.
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