Vacuole membrane contact sites and domains: emerging hubs to coordinate organelle function with cellular metabolism

2016 ◽  
Vol 44 (2) ◽  
pp. 528-533 ◽  
Author(s):  
Pedro Carpio Malia ◽  
Christian Ungermann
Keyword(s):  
Cellular Metabolism ◽  
Model System ◽  
Eukaryotic Cells ◽  
Lysosomal Function ◽  
Vacuole Membrane ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Vesicular Carriers ◽  
Membrane Contact ◽  
Cellular Organelles

Eukaryotic cells rely on a set of membrane-enclosed organelles to perform highly efficient reactions in an optimized environment. Trafficking of molecules via vesicular carriers and membrane contact sites (MCS) allow the coordination between these compartments, though the precise mechanisms are still enigmatic. Among the cellular organelles, the lysosome/vacuole stands out as a central hub, where multiple pathways merge. Importantly, the delivered material is degraded and the monomers are recycled for further usage, which explains its wide variety of roles in controlling cellular metabolism. We will highlight recent advances in the field by focusing on the yeast vacuole as a model system to understand lysosomal function in general.

Mitochondria–organelle contact sites: the plot thickens

2017 ◽  
Vol 45 (2) ◽  
pp. 477-488 ◽  
Author(s):  
Yael Elbaz-Alon
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cellular Metabolism ◽  
Close Apposition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Cellular Organelles

Membrane contact sites (MCSs) are areas of close apposition between the membranes of two different organelles that enable non-vesicular transfer of ions and lipids. Recent studies reveal that mitochondria maintain contact sites with organelles other than the endoplasmic reticulum such as the vacuole, plasma membrane and peroxisomes. This review focuses on novel findings achieved mainly in yeast regarding tethers, function and regulation of mitochondria–organelle contact sites. The emerging network of MCSs linking virtually all cellular organelles is highly dynamic and integrated with cellular metabolism.

Nucleus–vacuole junctions in yeast: anatomy of a membrane contact site

2006 ◽  
Vol 34 (3) ◽  
pp. 340-342 ◽  
Author(s):  
E. Kvam ◽  
D.S. Goldfarb
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Model System ◽  
Specific Interactions ◽  
Contact Site ◽  
Vacuole Membrane ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Unique Model ◽  
Membrane Contact ◽  
Autophagic Process

NV junctions (nucleus–vacuole junctions) in Saccharomyces cerevisiae are MCSs (membrane contact sites) formed through specific interactions between Vac8p on the vacuole membrane and Nvj1p in the outer nuclear membrane, which is continuous with the perinuclear ER (endoplasmic reticulum). NV junctions mediate a unique autophagic process that degrades portions of the yeast nucleus through a process called ‘piecemeal microautophagy of the nucleus’ (PMN). Our studies suggest that the lipid composition of NV junctions plays an important role in the biogenesis of PMN structures. NV junctions represent a unique model system for studying the biology of ER MCSs, as well as the molecular mechanism of selective microautophagy.

scholarly journals Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Composition ◽  
Sigma 1 Receptor ◽  
Functional Roles ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Sigma 1 ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

scholarly journals Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites

2016 ◽  
Vol 27 (15) ◽  
pp. 2435-2449 ◽  
Author(s):  
Jae-Sook Park ◽  
Mary K. Thorsness ◽  
Robert Policastro ◽  
Luke L. McGoldrick ◽  
Nancy M. Hollingsworth ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Protein Sorting ◽  
Growth Conditions ◽  
Eukaryotic Cells ◽  
Cellular Functions ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

The Vps13 protein family is highly conserved in eukaryotic cells. Mutations in human VPS13 genes result in a variety of diseases, such as chorea acanthocytosis (ChAc), but the cellular functions of Vps13 proteins are not well defined. In yeast, there is a single VPS13 orthologue, which is required for at least two different processes: protein sorting to the vacuole and sporulation. This study demonstrates that VPS13 is also important for mitochondrial integrity. In addition to preventing transfer of DNA from the mitochondrion to the nucleus, VPS13 suppresses mitophagy and functions in parallel with the endoplasmic reticulum–mitochondrion encounter structure (ERMES). In different growth conditions, Vps13 localizes to endosome–mitochondrion contacts and to the nuclear–vacuole junctions, indicating that Vps13 may function at membrane contact sites. The ability of VPS13 to compensate for the absence of ERMES correlates with its intracellular distribution. We propose that Vps13 is present at multiple membrane contact sites and that separation-of-function mutants are due to loss of Vps13 at specific junctions. Introduction of VPS13A mutations identified in ChAc patients at cognate sites in yeast VPS13 are specifically defective in compensating for the lack of ERMES, suggesting that mitochondrial dysfunction might be the basis for ChAc.

Building lipid ‘PIPelines’ throughout the cell by ORP/Osh proteins

2014 ◽  
Vol 42 (5) ◽  
pp. 1465-1470 ◽  
Author(s):  
Joachim Moser von Filseck ◽  
Bruno Mesmin ◽  
Joëlle Bigay ◽  
Bruno Antonny ◽  
Guillaume Drin
Keyword(s):  
Secretory Pathway ◽  
Eukaryotic Cells ◽  
Transport Mechanisms ◽  
Related Protein ◽  
Oxysterol Binding Protein ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Lipid Species ◽  
Membrane Contact ◽  
Phosphatidylinositol 4

In eukaryotic cells, a sterol gradient exists between the early and late regions of the secretory pathway. This gradient seems to rely on non-vesicular transport mechanisms mediated by specialized carriers. The oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) family has been assumed initially to exclusively include proteins acting as sterol sensors/transporters and many efforts have been made to determine their mode of action. Our recent studies have demonstrated that some ORP/Osh proteins are not mere sterol transporters, but sterol/phosphatidylinositol 4-phosphate [PI(4)P] exchangers. They exploit the PI(4)P gradient at the endoplasmic reticulum (ER)/Golgi interface, or at membrane-contact sites between these compartments, to actively create a sterol gradient. Other recent reports have suggested that all ORP/Osh proteins bind PI(4)P and recognize a second lipid that is not necessary sterol. We have thus proposed that ORP/Osh proteins use PI(4)P gradients between organelles to convey various lipid species.

The ERMES complex and ER–mitochondria connections

2012 ◽  
Vol 40 (2) ◽  
pp. 445-450 ◽  
Author(s):  
Agnès H. Michel ◽  
Benoît Kornmann
Keyword(s):  
Protein Complex ◽  
Biochemical Characterization ◽  
Eukaryotic Cell ◽  
Yeast Protein ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Synthetic Protein ◽  
Membrane Contact ◽  
Cellular Organelles

Cellular organelles need to communicate in order to co-ordinate homoeostasis of the compartmentalized eukaryotic cell. Such communication involves the formation of membrane contact sites between adjacent organelles, allowing privileged exchange of metabolites and information. Using a synthetic protein designed to artificially tether the ER (endoplasmic reticulum) to mitochondria, we have discovered a yeast protein complex naturally involved in establishing and maintaining contact sites between these two organelles. This protein complex is physiologically involved in a plethora of mitochondrial processes, suggesting that ER–mitochondria connections play a central co-ordinating role in the regulation of mitochondrial biology. Recent biochemical characterization of this protein complex led to the discovery that GTPases of the Miro family are part of ER–mitochondria connections. The yeast Miro GTPase Gem1 localizes to ER–mitochondria interface and influences the size and distribution of mitochondria. Thus Miro GTPases may serve as regulators of the ER–mitochondria connection.

scholarly journals The Vps13 Family of Lipid Transporters and Its Role at Membrane Contact Sites

2021 ◽  
Vol 22 (6) ◽  
pp. 2905
Author(s):  
Samantha Katarzyna Dziurdzik ◽  
Elizabeth Conibear
Keyword(s):  
Neurological Disorders ◽  
Model System ◽  
Lipid Transport ◽  
Direct Channel ◽  
Large Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
New Family ◽  
Lipid Transporters ◽  
Membrane Contact

The conserved VPS13 proteins constitute a new family of lipid transporters at membrane contact sites. These large proteins are suspected to bridge membranes and form a direct channel for lipid transport between organelles. Mutations in the 4 human homologs (VPS13A–D) are associated with a number of neurological disorders, but little is known about their precise functions or the relevant contact sites affected in disease. In contrast, yeast has a single Vps13 protein which is recruited to multiple organelles and contact sites. The yeast model system has proved useful for studying the function of Vps13 at different organelles and identifying the localization determinants responsible for its membrane targeting. In this review we describe recent advances in our understanding of VPS13 proteins with a focus on yeast research.

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