Of yeast, mice and men: MAMs come in two flavors

Abstract

The past decade has seen dramatic progress in our understanding of membrane contact sites (MCS). Important examples of these are endoplasmic reticulum (ER)-mitochondria contact sites. ER-mitochondria contacts have originally been discovered in mammalian tissue, where they have been designated as mitochondria-associated membranes (MAMs). It is also in this model system, where the first critical MAM proteins have been identified, including MAM tethering regulators such as phospho-furin acidic cluster sorting protein 2 (PACS-2) and mitofusin-2. However, the past decade has seen the discovery of the MAM also in the powerful yeast model system Saccharomyces cerevisiae. This has led to the discovery of novel MAM tethers such as the yeast ER-mitochondria encounter structure (ERMES), absent in the mammalian system, but whose regulators Gem1 and Lam6 are conserved. While MAMs, sometimes referred to as mitochondria-ER contacts (MERCs), regulate lipid metabolism, Ca2+ signaling, bioenergetics, inflammation, autophagy and apoptosis, not all of these functions exist in both systems or operate differently. This biological difference has led to puzzling discrepancies on findings obtained in yeast or mammalian cells at the moment. Our review aims to shed some light onto mechanistic differences between yeast and mammalian MAM and their underlying causes. Reviewers: This article was reviewed by Paola Pizzo (nominated by Luca Pellegrini), Maya Schuldiner and György Szabadkai (nominated by Luca Pellegrini).