Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death.
Programmed cell death (PCD) is essential for normal development and maintenance of tissue homeostasis in multicellular organisms. While it is now evident that PCD can take many different forms, apoptosis is probably the most well-defined cell death programme. The characteristic morphological and biochemical features associated with this highly regulated form of cell death have until recently been exclusively attributed to the caspase family of cysteine proteases. As a result, many investigators affiliate apoptosis with its pivotal execution system, i.e. caspase activation. However, it is becoming increasingly clear that PCD or apoptosis can also proceed in a caspase-independent manner and maintain key characteristics of apoptosis. Mitochondrial integrity is central to both caspase-dependent and-independent cell death. The release of pro-apoptotic factors from the mitochondrial intermembrane space is a key event in a cell's commitment to die and is under the tight regulation of the Bcl-2 family. However, the underlying mechanisms governing the efflux of these pro-death molecules are largely unknown. This review will focus on the regulation of mitochondrial integrity by Bcl-2 family members with particular attention to the controlled release of factors involved in caspase-independent cell death.
Cell Development and Disease, Biochemistry Department, Biosciences Institute, National University of Ireland, Cork, Ireland.
Maryanne
M
Donovan
Thomas G
TG
Cotter
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D020169:Caspases / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005420:Flavoproteins / Q000502:physiology; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000502:physiology; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004706:Endodeoxyribonucleases; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2; D020169:Caspases