Life, death and burial: Multifaceted impact of autophagy

Lorenzo Galluzzi, Eugenia Morselli, José Miguel Vicencio, Oliver Kepp, Nicholas Joza, Nicolas Tajeddine, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Macroautophagy, often referred to as autophagy, designates the process by which portions of the cytoplasm, intracellular ofganelles and long-lived proteins are engulfed in double-membraned vacuoles (autophagosomes) and sent for lysosomal degradation. Basal levels of autophagy contribute to the maintenance of intracellular homoeostasis by ensuring the turnover of supernumerary, aged and/or damaged components. Under conditions of starvation, the autophagic pathway operates to supply cells with metabolic substrates, and hence represents an important pro-survival mechanism. Moreover, autophagy is required for normal development and for the protective response to intracellular pathogens. Conversely, uncontrolled autophagy is associated with a particular type of cell death (termed autophagic, or type II) that is characterized by the massive accumulation of autophagosomes. Regulators of apoptosis (e.g. Bcl-2 family members) also modulate autophagy, suggesting an intimate cross-talk between these two degradative pathways. It is still unclear whether autophagic vacuolization has a causative role in cell death or whether it represents the ultimate attempt of cells to cope with lethal stress. For a multicellular organism, autophagic cell death might well represent a pro-survival mechanism, by providing metabolic supplies during whole-body nutrient deprivation. Alternatively, type II cell death might contribute to the disposal of cell corpses when heterophagy is deficient. Here, we briefly review the roles of autophagy in cell death and its avoidance.

Original languageEnglish
Pages (from-to)786-790
Number of pages5
JournalBiochemical Society Transactions
Volume36
Issue number5
DOIs
StatePublished - Oct 2008
Externally publishedYes

Keywords

  • Apoptosis
  • atg gene
  • Bcl-2
  • Beclin 1
  • Macroautophagy
  • Mitochondrion

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