A revolution in apoptosis: from a nucleocentric to a mitochondriocentric perspective.
In contrast to previous belief, it is now generally assumed that nuclear alterations constitute a sign rather than a mechanism of apoptosis. Until recently, research on apoptosis has been marked by three additional incorrect premises, namely that (1) mitochondria are not important for the regulation of cell death; (2) apoptosis is a linear sequence of molecular events in which clearly different effectors participate in pro-apoptotic signal transduction and apoptosis execution; and (3) apoptosis is fundamentally different from necrosis. Recent experimental data shed doubts on these notions, and rather suggest that (1) mitochondria exert a decisive role in cell death control; (2) apoptosis is likely to involve self-amplifying feedback loops in which the same molecule or process can participate at several levels; and (3) apoptosis and necrosis share a common pathway. These notions are changing the perception of the apoptotic process and will affect the exploration of age-associated alterations in cell death control.
Brenner
C
C
Centre National de la Recherche Scientifique, UPR420, Villejuif, France.
Marzo
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I
Kroemer
G
G
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009336:Necrosis; D010539:Permeability