Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release

Abstract

The distribution of the pro-apoptotic protein Bax in the outer mi-tochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signaling processes. We addressed a possible role of these domains, called Mitochon-dria-Associated Membranes (MAMs) in Bax localization and function, by ex-pressing the human protein in a yeast mutant deleted of MDM34, a ERMES (ER-Mitochondria Encounter Structure) component. By affecting MAMs stabil-ity, the deletion of MDM34 altered Bax mitochondrial localization, and de-creased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an incompletely released, MAMs-associated pool of cytochrome c.