Molecular mechanisms of regulated necrosis Review uri icon

Overview

MeSH Major

  • Membrane Potential, Mitochondrial
  • Models, Biological
  • Necrosis
  • Signal Transduction

abstract

  • It is now clear that apoptosis does not constitute the sole genetically encoded form of cell death. Rather, cells can spontaneously undertake or exogenously be driven into a cell death subroutine that manifests with necrotic features, yet can be inhibited by pharmacological and genetic interventions. As regulated necrosis (RN) plays a major role in both physiological scenarios (e.g., embryonic development) and pathological settings (e.g., ischemic disorders), consistent efforts have been made throughout the last decade toward the characterization of the molecular mechanisms that underlie this cell death modality. Contrarily to initial beliefs, RN does not invariably result from the activation of a receptor interacting protein kinase 3 (RIPK3)-dependent signaling pathway, but may be ignited by distinct molecular networks. Nowadays, various types of RN have been characterized, including (but not limited to) necroptosis, mitochondrial permeability transition (MPT)-dependent RN and parthanatos. Of note, the inhibition of only one of these modules generally exerts limited cytoprotective effects in vivo, underscoring the degree of interconnectivity that characterizes RN. Here, we review the signaling pathways, pathophysiological relevance and therapeutic implications of the major molecular cascades that underlie RN.

publication date

  • January 2014

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.semcdb.2014.02.006

PubMed ID

  • 24582829

Additional Document Info

start page

  • 24

end page

  • 32

volume

  • 35