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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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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

Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.

TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
Journal ArticleDOI

Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked

TL;DR: One possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria, which is normally located in the mitochondrial intermembrane space.
Journal ArticleDOI

The BCL-2 protein family: opposing activities that mediate cell death

TL;DR: New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
Journal ArticleDOI

Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death

TL;DR: In this article, the authors found that doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin.
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