Apoptosis is physiologic cell death program that is indispensable for the development and maintenance of multicellular organisms. Dysfunction of this genetically controlled pathway can trigger an inappropriate excess or lack of cell death, thereby leading to pathological disorders as diverse as cancer, diabetes, obesity, ischemia-reperfusion injury and neurodegenerative disorders.

In vertebrates, normal or pathological cell death is mostly conducted through the induction of the mitochondrial apoptotic pathway, leading to "the point of no return"-mitochondrial outer membrane permeabilization (MOMP).  This event, mainly regulated by the different members of the Bcl-2 family of proteins (such as BimS), results in the dismantling of the cell, via the release of cytochrome c from the mitochondrial compartment into the cytosol.
    
To study the direct effect of MOMP on cell physiology, we generated a molecular tool capable of triggering a specific, rapid and convenient induction of MOMP in the absence of other nonspecific apoptotic signaling pathways.  To accomplish this, we fused the "BH3-only" protein Bims to a domain of the Estrogen Receptor (ER).  This 4-hydroxytamoxifen (OHT) responsive protein was stably introduced into human embryonic kidney cells. We have recently generated cells stably expressing both Bims-ER / mtDsRed and cytochrome c-GFP.  Preliminary results show that upon OHT treatment, Bims-ER expressing cells induce the release of cytochrome c from mitochondria (Cf. movie) and cell death. 

Understanding molecular events responsible for apoptosis will contribute in a long term to define new potent therapeutic drugs interfering with excess or lack of cell death and hopefully treat these severe pathological troubles.