The Endoplasmic Reticulum-Mitochondria Encounter Structure and its Regulatory Proteins

Contact ◽

10.1177/25152564211064491 ◽

2021 ◽

Vol 4 ◽

pp. 251525642110644

Author(s):

Javairia Y. Cheema ◽

Jiajia He ◽

Wenfan Wei ◽

Chuanhai Fu

Keyword(s):

Endoplasmic Reticulum ◽

Regulatory Proteins ◽

Contact Sites ◽

Constitutive Components ◽

And Function

In fungi, the endoplasmic reticulum-mitochondria encounter structure (ERMES) is present between the endoplasmic reticulon (ER) and mitochondria to promote the formation of the ER-mitochondria contact sites. Four constitutive components (Mmm1, Mdm12, Mdm34, and Mdm10) assemble to form the ERMES complex while regulator proteins are required for regulating the organization and function of the ERMES complex. Multiple regulator proteins, including Gem1, Lam6, Tom7, and Emr1, of the ERMES complex, have been identified recently. In this review, we discuss the organization of the ERMES complex and the roles of the regulator proteins of the ERMES complex.

Download Full-text

A small GTPase involved in mitochondrial morphology and function

Biochemical Society Transactions ◽

10.1042/bst20140284 ◽

2015 ◽

Vol 43 (1) ◽

pp. 108-110 ◽

Cited By ~ 2

Author(s):

Anne Spang

Keyword(s):

Endoplasmic Reticulum ◽

Golgi Complex ◽

Essential Role ◽

Small Gtpase ◽

Mitochondrial Morphology ◽

Interconnected Network ◽

Contact Sites ◽

Close Proximity ◽

And Function ◽

Adp Ribosylation Factor

Mitochondria are the powerhouse of cells as they produce the bulk of ATP which is consumed by the cell. They form a highly interconnected network that is governed by fission and fusion processes. In addition, mitochondria and the endoplasmic reticulum (ER) are found in close proximity to each other and it is thought that they maintain contact sites to exchange molecules. The regulation and the function of these contact sites need to be further explored. The small GTPase Arf1 (ADP-ribosylation factor 1), which is best known for its essential role in the generation of coatomer protein I (COPI)-coated vesicles at the Golgi complex appears to be also essential for the dynamics and maintenance of mitochondrial function, presumably at ER–mitochondrial contact sites.

Download Full-text

SAC1 Degrades its Lipid Substrate PtdIns4P in the Endoplasmic Reticulum to Maintain a Steep Chemical Gradient with Donor Membranes

10.1101/258087 ◽

2018 ◽

Author(s):

James P. Zewe ◽

Rachel C. Wills ◽

Sahana Sangappa ◽

Brady D. Goulden ◽

Gerald R. V. Hammond

Keyword(s):

Endoplasmic Reticulum ◽

Lipid Homeostasis ◽

Chemical Gradient ◽

Vesicular Traffic ◽

Membrane Contact Sites ◽

Contact Sites ◽

Catalytic Domains ◽

In Trans ◽

Membrane Contact ◽

And Function

AbstractGradients of PtdIns4P between organelle membranes and the endoplasmic reticulum (ER) are thought to drive counter-transport of other lipids via non-vesicular traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4P in a “cis” configuration at the ER to maintain the gradient. However, SAC1 has also been proposed to act in “trans” at membrane contact sites, which could oppose lipid traffic. It is therefore crucial to determine which mode SAC1 uses in living cells. We report that acute inhibition of SAC1 causes accumulation of PtdIns4P in the ER, that SAC1 does not enrich at membrane contact sites, and that SAC1 has little activity in “trans”, unless a linker is added between its ER-anchored and catalytic domains. The data reveal an obligate “cis” activity of SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid traffic more broadly in inositol lipid homeostasis and function.

Download Full-text

SAC1 degrades its lipid substrate PtdIns4P in the endoplasmic reticulum to maintain a steep chemical gradient with donor membranes

eLife ◽

10.7554/elife.35588 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 46

Author(s):

James P Zewe ◽

Rachel C Wills ◽

Sahana Sangappa ◽

Brady D Goulden ◽

Gerald RV Hammond

Keyword(s):

Endoplasmic Reticulum ◽

Lipid Homeostasis ◽

Chemical Gradient ◽

Vesicular Traffic ◽

Membrane Contact Sites ◽

Contact Sites ◽

Catalytic Domains ◽

In Trans ◽

Membrane Contact ◽

And Function

Gradients of PtdIns4P between organelle membranes and the endoplasmic reticulum (ER) are thought to drive counter-transport of other lipids via non-vesicular traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4P in a ‘cis’ configuration at the ER to maintain the gradient. However, SAC1 has also been proposed to act in ‘trans’ at membrane contact sites, which could oppose lipid traffic. It is therefore crucial to determine which mode SAC1 uses in living cells. We report that acute inhibition of SAC1 causes accumulation of PtdIns4P in the ER, that SAC1 does not enrich at membrane contact sites, and that SAC1 has little activity in ‘trans’, unless a linker is added between its ER-anchored and catalytic domains. The data reveal an obligate ‘cis’ activity of SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid traffic more broadly in inositol lipid homeostasis and function.

Download Full-text

Structure of contact sites between the outer and inner mitochondrial membranes investigated by HVEM tomography

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100167299 ◽

1996 ◽

Vol 54 ◽

pp. 966-967

Author(s):

C.A. Mannella ◽

K.F. Buttle ◽

K.A. O‘Farrell ◽

A. Leith ◽

M. Marko

Keyword(s):

Liver Mitochondrion ◽

Adenine Nucleotide ◽

Protein Complexes ◽

Mitochondrial Membranes ◽

Electron Microscopic ◽

Contact Sites ◽

Transmission Electron ◽

Precursor Proteins ◽

Membrane Contacts ◽

And Function

Early transmission electron microscopy of plastic-embedded, thin-sectioned mitochondria indicated that there are numerous junctions between the outer and inner membranes of this organelle. More recent studies have suggested that the mitochondrial membrane contacts may be the site of protein complexes engaged in specialized functions, e.g., import of mitochondrial precursor proteins, adenine nucleotide channeling, and even intermembrane signalling. It has been suggested that the intermembrane contacts may be sites of membrane fusion involving non-bilayer lipid domains in the two membranes. However, despite growing interest in the nature and function of intramitochondrial contact sites, little is known about their structure.We are using electron microscopic tomography with the Albany HVEM to determine the internal organization of mitochondria. We have reconstructed a 0.6-μm section through an isolated, plasticembedded rat-liver mitochondrion by combining 123 projections collected by tilting (+/- 70°) around two perpendicular tilt axes. The resulting 3-D image has confirmed the basic inner-membrane organization inferred from lower-resolution reconstructions obtained from single-axis tomography.

Download Full-text

Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease

The Journal of Membrane Biology ◽

10.1007/s00232-021-00184-z ◽

2021 ◽

Author(s):

Vitalii Kryvenko ◽

Olga Vagin ◽

Laura A. Dada ◽

Jacob I. Sznajder ◽

István Vadász

Keyword(s):

Endoplasmic Reticulum ◽

Intracellular Signaling ◽

Loss Of Function ◽

Α Subunit ◽

Rate Limiting Step ◽

Atpase Subunits ◽

A Cell ◽

Health And Disease ◽

And Function ◽

Rate Limiting

Abstract The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions. Graphic Abstract

Download Full-text

Synaptotagmins at the endoplasmic reticulum–plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress

The Plant Cell ◽

10.1093/plcell/koab122 ◽

2021 ◽

Author(s):

Noemi Ruiz-Lopez ◽

Jessica Pérez-Sancho ◽

Alicia Esteban del Valle ◽

Richard P Haslam ◽

Steffen Vanneste ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Plasma Membrane ◽

Abiotic Stress ◽

Fluorescent Protein ◽

Mechanical Damage ◽

Membrane Contact Sites ◽

Contact Sites ◽

Membrane Contact ◽

Green Fluorescent

Abstract Endoplasmic reticulum-plasma membrane contact sites (ER-PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER-PM protein tether synaptotagmin1 (SYT1) exhibit decreased plasma membrane (PM) integrity under multiple abiotic stresses such as freezing, high salt, osmotic stress and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER-PM tether that also functions in maintaining PM integrity. The ER-PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild type while the levels of most glycerolipid species remain unchanged. Additionally, the SYT1-green fluorescent protein (GFP) fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.

Download Full-text

New horizons in mitochondrial contact site research

Biological Chemistry ◽

10.1515/hsz-2020-0133 ◽

2020 ◽

Vol 401 (6-7) ◽

pp. 793-809

Author(s):

Naama Zung ◽

Maya Schuldiner

Keyword(s):

Endoplasmic Reticulum ◽

Molecular Mechanisms ◽

Contact Site ◽

New Horizons ◽

Contact Sites ◽

Future Goals ◽

Close Proximity ◽

Recent Developments ◽

Site Field ◽

First Contact

AbstractContact sites, areas where two organelles are held in close proximity through the action of molecular tethers, enable non-vesicular communication between compartments. Mitochondria have been center stage in the contact site field since the discovery of the first contact between mitochondria and the endoplasmic reticulum (ER) over 60 years ago. However, only now, in the last decade, has there been a burst of discoveries regarding contact site biology in general and mitochondrial contacts specifically. The number and types of characterized contacts increased dramatically, new molecular mechanisms enabling contact formation were discovered, additional unexpected functions for contacts were shown, and their roles in cellular and organismal physiology were emphasized. Here, we focus on mitochondria as we highlight the most recent developments, future goals and unresolved questions in the field.

Download Full-text

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽

10.1177/25152564211026505 ◽

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.

Download Full-text