Bcl-2 on the endoplasmic reticulum: protecting the mitochondria from a distance.
Bcl-2 has been described both as an inhibitor of programmed cell death and as an inhibitor of mitochondrial dysfunction during apoptosis. It is still not clear what biochemical activity of Bcl-2 is responsible for its function, but increasing evidence indicates that a functional activity of Bcl-2 on the endoplasmic reticulum (ER) protects mitochondria under diverse circumstances. Indeed, an emerging hypothesis is that, during apoptosis, the Bcl-2 family regulates ER-to-mitochondrion communication by BH3-only proteins and calcium ions and thereby triggers mitochondrial dysfunction and cell death.
Departments of Medicine and Pharmacology, Comprehensive Cancer Center, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Michael J
MJ
Thomenius
Clark W
CW
Distelhorst
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D045304:Cytochromes c; D020169:Caspases