The ERMES complex and ER–mitochondria connections

2012 ◽  
Vol 40 (2) ◽  
pp. 445-450 ◽  
Author(s):  
Agnès H. Michel ◽  
Benoît Kornmann

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.

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny

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.


2017 ◽  
Vol 45 (2) ◽  
pp. 477-488 ◽  
Author(s):  
Yael Elbaz-Alon

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.


2016 ◽  
Vol 44 (2) ◽  
pp. 528-533 ◽  
Author(s):  
Pedro Carpio Malia ◽  
Christian Ungermann

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.


2020 ◽  
Vol 118 (3) ◽  
pp. 574a
Author(s):  
Matthias Garten ◽  
Josh Beck ◽  
Robyn Roth ◽  
John E. Heuser ◽  
Tatyana Tenkova-Heuser ◽  
...  

Genetics ◽  
2021 ◽  
Author(s):  
Christopher A Piggott ◽  
Zilu Wu ◽  
Stephen Nurrish ◽  
Suhong Xu ◽  
Joshua M Kaplan ◽  
...  

Abstract The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole C. elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 co-localizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68/RyR calcium channel, and is required for animal movement. In neurons, JPH-1 co-localizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell non-autonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and unc-68/RyR for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68/RyR is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.


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