Intracellular calcium stores and programmed cell death.

Apoptosis is an evolutionary conserved programmed cell-death pathway designed to remove extraneous or damaged cells without inducing inflammation. The intrinsic pathway of apoptosis is regulated by proteins of the Bcl2 family. Bax inhibitor-1 (BI-1) is an evolutionary conserved cytoprotective protein, which is localized in the endoplasmic reticulum (ER) and is structurally and functionally unrelated to the Bcl2 family. Another anti-apoptotic protein related to BI-1 is the Golgi anti-apoptotic protein (GAAP), which is located in the Golgi compartment. In this project we will focus on the role of organellar Ca2+ homeostasis in apoptosis. We will investigate the effects on ER Ca2+ fluxes of particular members of the Bcl2-family proteins, for which evidence has been obtained that they are localized in the ER and that part of their signaling is targeted to the ER. We will analyze the regulation of intracellular Ca2+ dynamics by BI-1 and GAAP in order to unravel the cellular mechanism of this new type of anti-apoptotic proteins.

Keywords:Cell death

Disciplines:Biochemistry and metabolism, Medical biochemistry and metabolism