P3, Ana J. Garcia Saez

Interplay between the Bcl-2 proteins and Drp1:

a biophysical characterization

A key step in the signaling pathway of apoptosis is MOM permeabilization, which is considered the point-of-no-return in the cell’s commitment to death. Bax is a protein of the Bcl-2 family that directly mediates MOM permeabilization. The machinery for mitochondrial fusion and fission has been shown to also play a role in the regulation of MOM permeabilization, likely by affecting the function of Bax, and vice versa. Drp1 is a large GTPase of the dynamin family that is necessary for mitochondrial division in mammals. During apoptosis, mitochondria undergo massive fragmentation accompanying MOM permeabilization. Interestingly, Bax and Drp1 colocalize at discrete MOM foci that likely correlate with mitochondria/ER contact sites. However, the molecular details and functional consequences of the interplay between Bax and Drp1 remain unresolved.

The main objective of this project is to uncover the molecular mechanism of the interaction between Bax and Drp1 and to correlate it with cellular function. To this aim, we will used functional and single molecule microscopy to understand the structural organization of Bax/Drp1 complexes, including their binding interfaces, and to shed light on the functional consequences of the interaction.

Garcia Saez group Webpage