Organelle-specific initiation of cell death


In a majority of pathophysiological settings, cell death is not accidental — it is controlled by a complex molecular apparatus. Such a system operates like a computer: it receives several inputs that inform on the current state of the cell and the extracellular microenvironment, integrates them and generates an output. Thus, depending on a network of signals generated at specific subcellular sites, cells can respond to stress by attemptinwg to recover homeostasis or by activating molecular cascades that lead to cell death by apoptosis or necrosis. Here, we discuss the mechanisms whereby cellular compartments — including the nucleus, mitochondria, plasma membrane, endoplasmic reticulum, Golgi apparatus, lysosomes, cytoskeleton and cytosol — sense homeostatic perturbations and translate them into a cell-death-initiating signal.

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Figure 1: General organization of organelle-specific responses to stress.
Figure 2: Major pathways of cell death initiation by the nucleus.
Figure 3: Major pathways of cell death initiation by the plasma membrane.
Figure 4: Major pathways of cell death initiation by lysosomes.


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We apologise to the scientists working in this area for being unable to cite here the huge amount of top-quality literature dealing with the organelle-specific initiation of cell death. Authors are supported by the Ligue contre le Cancer (équipe labelisée); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; AXA Chair for Longevity Research; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).

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L.G. and J.M.B-S.P contributed equally to this work. L.G. and G.K. jointly supervised this work.

Correspondence to Lorenzo Galluzzi or Guido Kroemer.

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Galluzzi, L., Bravo-San Pedro, J. & Kroemer, G. Organelle-specific initiation of cell death. Nat Cell Biol 16, 728–736 (2014).

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