IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond.
Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) serve to discharge Ca(2+) from ER stores in response to agonist stimulation. The present review summarizes the role of these receptors in models of Ca(2+)-dependent apoptosis. In particular we focus on the regulation of IP(3)Rs by caspase-3 cleavage, cytochrome c, anti-apoptotic proteins and Akt kinase. We also address the evidence that some of the effects of IP(3)Rs in apoptosis may be independent of their ion-channel function. The role of IP(3)Rs in delivering Ca(2+) to the mitochondria is discussed from the perspective of the factors determining inter-organellar dynamics and the spatial proximity of mitochondria and ER membranes.
Joseph
Suresh K
SK
Department of Pathology & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. suresh.joseph@mail.tju.edu
Hajnóczky
György
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology
D053496:Inositol 1,4,5-Trisphosphate Receptors; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium