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 mitochondrial 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 signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.