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Of yeast, mice and men: MAMs come in two flavors
Maria Sol Herrera-Cruz1, Thomas Simmen2
1Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G2H7, Canada.
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).
Insights
Membrane contact sites (MCS) between the endoplasmic reticulum and mitochondria, known as MAMs, have distinct mechanisms in yeast and mammals. This review explores these differences to resolve conflicting research findings.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- Membrane contact sites (MCS) are crucial for cellular functions.
- Endoplasmic reticulum (ER)-mitochondria contact sites, termed mitochondria-associated membranes (MAMs), were first identified in mammals.
- MAMs have since been discovered in yeast (Saccharomyces cerevisiae), revealing novel tethering complexes like ERMES.
Purpose of the Study:
- To review and compare the mechanistic differences between yeast and mammalian MAMs.
- To elucidate the underlying causes of discrepancies in findings between these model systems.
- To provide insights into the conserved and divergent functions of ER-mitochondria contacts.
Main Methods:
- Comparative analysis of literature on MAMs in yeast and mammalian systems.
- Identification and discussion of key MAM proteins and tethering complexes (e.g., PACS-2, mitofusin-2, ERMES, Gem1, Lam6).
- Examination of functional differences in lipid metabolism, Ca2+ signaling, and other processes.
Main Results:
- Mammalian and yeast MAMs exhibit significant mechanistic variations.
- Novel yeast-specific tethers (ERMES) and conserved regulators (Gem1, Lam6) have been identified.
- Functional roles of MAMs, including lipid metabolism and Ca2+ signaling, differ between species.
Conclusions:
- Understanding species-specific MAM mechanisms is essential for reconciling research.
- Divergent MAM structures and functions impact cellular processes differently in yeast and mammals.
- Further research is needed to fully characterize the conserved and unique aspects of ER-mitochondria communication.
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