scholarly journals Contact-ID, a tool for profiling organelle contact sites, reveals regulatory proteins of mitochondrial-associated membrane formation

2020 ◽  
Vol 117 (22) ◽  
pp. 12109-12120 ◽  
Author(s):  
Chulhwan Kwak ◽  
Sanghee Shin ◽  
Jong-Seok Park ◽  
Minkyo Jung ◽  
Truong Thi My Nhung ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Regulatory Proteins ◽  
Live Cells ◽  
Strong Activity ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Specific Proteins ◽  
Molecular Components ◽  
Organelle Membrane

The mitochondria-associated membrane (MAM) has emerged as a cellular signaling hub regulating various cellular processes. However, its molecular components remain unclear owing to lack of reliable methods to purify the intact MAM proteome in a physiological context. Here, we introduce Contact-ID, a split-pair system of BioID with strong activity, for identification of the MAM proteome in live cells. Contact-ID specifically labeled proteins proximal to the contact sites of the endoplasmic reticulum (ER) and mitochondria, and thereby identified 115 MAM-specific proteins. The identified MAM proteins were largely annotated with the outer mitochondrial membrane (OMM) and ER membrane proteins with MAM-related functions: e.g., FKBP8, an OMM protein, facilitated MAM formation and local calcium transport at the MAM. Furthermore, the definitive identification of biotinylation sites revealed membrane topologies of 85 integral membrane proteins. Contact-ID revealed regulatory proteins for MAM formation and could be reliably utilized to profile the proteome at any organelle–membrane contact sites in live cells.

scholarly journals Relevance of Membrane Contact Sites in Cancer Progression

2021 ◽  
Vol 8 ◽  
Author(s):  
Aurora Gil-Hernández ◽  
Miguel Arroyo-Campuzano ◽  
Arturo Simoni-Nieves ◽  
Cecilia Zazueta ◽  
Luis Enrique Gomez-Quiroz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Lipid Signaling ◽  
Cell Physiology ◽  
Vesicular Traffic ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Diagnostic Potential ◽  
Specific Proteins ◽  
Membrane Contact

Membrane contact sites (MCS) are typically defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins. The study of MCS is considered as an emergent field that shows how crucial organelle interactions are in cell physiology. MCS regulate a myriad of physiological processes such as apoptosis, calcium, and lipid signaling, just to name a few. The membranal interactions between the endoplasmic reticulum (ER)–mitochondria, the ER–plasma membrane, and the vesicular traffic have received special attention in recent years, particularly in cancer research, in which it has been proposed that MCS regulate tumor metabolism and fate, contributing to their progression. However, as the therapeutic or diagnostic potential of MCS has not been fully revisited, in this review, we provide recent information on MCS relevance on calcium and lipid signaling in cancer cells and on its role in tumor progression. We also describe some proteins associated with MCS, like CERT, STIM1, VDAC, and Orai, that impact on cancer progression and that could be a possible diagnostic marker. Overall, these information might contribute to the understanding of the complex biology of cancer cells.

scholarly journals Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 598 ◽  
Author(s):  
Anna Picca ◽  
Riccardo Calvani ◽  
Hélio José Coelho-Junior ◽  
Francesco Landi ◽  
Roberto Bernabei ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Age Related ◽  
Bidirectional Communication ◽  
Membrane Contact ◽  
Organelle Membrane

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson’s disease as a prototypical geroscience condition.

The role of phosphatidylinositol-transfer proteins at membrane contact sites

2016 ◽  
Vol 44 (2) ◽  
pp. 419-424 ◽  
Author(s):  
Michael Selitrennik ◽  
Sima Lev
Keyword(s):  
Underlying Mechanism ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Compartments ◽  
Potential Mode ◽  
Membrane Contact ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol Transfer Proteins

Phosphatidylinositol-transfer proteins (PITPs) have been initially identified as soluble factors that accelerate the monomeric exchange of either phosphatidylinositol (PI) or phosphatidylcholine (PC) between membrane bilayers in vitro. They are highly conserved in eukaryotes and have been implicated in different cellular processes, including vesicular trafficking, signal transduction, and lipid metabolism. Recent studies suggest that PITPs function at membrane contact sites (MCSs) to facilitate the transport of PI from its synthesis site at the endoplasmic reticulum (ER) to various membrane compartments. In this review, we describe the underlying mechanism of PITPs targeting to MCSs, discuss their cellular roles and potential mode of action.

Triggering of Ca2+ signals by NAADP-gated two-pore channels: a role for membrane contact sites?

2012 ◽  
Vol 40 (1) ◽  
pp. 153-157 ◽  
Author(s):  
Sandip Patel ◽  
Eugen Brailoiu
Keyword(s):  
Endoplasmic Reticulum ◽  
Nicotinic Acid ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Acidic Organelles ◽  
Specific Membrane ◽  
Ca2 Channels

NAADP (nicotinic acid–adenine dinucleotide phosphate) is a potent Ca2+-mobilizing messenger implicated in many Ca2+-dependent cellular processes. It is highly unusual in that it appears to trigger Ca2+ release from acidic organelles such as lysosomes. These signals are often amplified by archetypal Ca2+ channels located in the endoplasmic reticulum. Recent studies have converged on the TPCs (two-pore channels) which localize to the endolysosomal system as the likely primary targets through which NAADP mediates its effects. ‘Chatter’ between TPCs and endoplasmic reticulum Ca2+ channels is disrupted when TPCs are directed away from the endolysosomal system. This suggests that intracellular Ca2+ release channels may be closely apposed, possibly at specific membrane contact sites between acidic organelles and the endoplasmic reticulum.

scholarly journals The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites

2016 ◽  
Vol 44 (2) ◽  
pp. 447-451 ◽  
Author(s):  
Shweta Yadav ◽  
Shamshad Cockcroft ◽  
Padinjat Raghu
Keyword(s):  
Membrane Composition ◽  
Contact Site ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Physiological Processes ◽  
Specific Proteins ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Cellular Compartments

Several recent studies have demonstrated the existence of membrane contact sites (MCS) between intracellular organelles in eukaryotic cells. Recent exciting studies have also demonstrated the existence of biomolecular interactions at these contact sites in mediating changes in the membrane composition of the cellular compartments. However, the role of such contact sites in regulating organelle function and physiological processes remains less clear. In this review we discuss the existence of a contact site between the plasma membrane (PM) and the endoplasmic reticulum (ER) in Drosophila photoreceptors. Further, we discuss the role of specific proteins present at this location in regulating phospholipid turnover and its impact in regulating a physiological process, namely phototransduction.

scholarly journals Endoplasmic Reticulum–Plasma Membrane Contact Sites: Regulators, Mechanisms, and Physiological Functions

2021 ◽  
Vol 9 ◽  
Author(s):  
Chenlu Li ◽  
Tiantian Qian ◽  
Ruyue He ◽  
Chun Wan ◽  
Yinghui Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Lipid Homeostasis ◽  
Ion Dynamics ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Intracellular Signals ◽  
Membrane Contact ◽  
External Stimuli

The endoplasmic reticulum (ER) forms direct membrane contact sites with the plasma membrane (PM) in eukaryotic cells. These ER-PM contact sites play essential roles in lipid homeostasis, ion dynamics, and cell signaling, which are carried out by protein-protein or protein-lipid interactions. Distinct tethering factors dynamically control the architecture of ER-PM junctions in response to intracellular signals or external stimuli. The physiological roles of ER-PM contact sites are dependent on a variety of regulators that individually or cooperatively perform functions in diverse cellular processes. This review focuses on proteins functioning at ER-PM contact sites and highlights the recent progress in their mechanisms and physiological roles.

scholarly journals Inter-organelle membrane contact sites: implications for lipid metabolism

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jean E. Vance
Keyword(s):  
Endoplasmic Reticulum Membrane ◽  
Biological Functions ◽  
Advantages And Disadvantages ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Experimental Approaches ◽  
Initial Discovery ◽  
Membrane Contact ◽  
Definition Of ◽  
Organelle Membrane

Abstract This article supplements a recent Perspective by Scorrano et al. in Nature Communications [10 [ (1)]:1287] in which the properties and functions of inter-organelle membrane contact sites were summarized. It is now clear that inter-organelle membrane contact sites are widespread in eukaryotic cells and that diverse pairs of organelles can be linked via unique protein tethers. An appropriate definition of what constitutes an inter-organelle membrane contact site was proposed in the Perspective. In addition, the various experimental approaches that are frequently used to study these organelle associations, as well as the advantages and disadvantages of each of these methods, were considered. The nature of the tethers that link the pairs of organelles at the contact sites was discussed in detail and some biological functions that have been ascribed to specific membrane contact sites were highlighted. Nevertheless, the functions of most types of organelle contact sites remain unclear. In the current article I have considered some of the points raised in the Perspective but have omitted detailed information on the roles of membrane contact sites in biological functions such as apoptosis, autophagy, calcium homeostasis and mitochondrial fusion. Instead, I have provided some background on the initial discovery of mitochondria-endoplasmic reticulum membrane contact sites, and have focussed on the known roles of membrane contact sites in inter-organelle lipid transport. In addition, potential roles for membrane contact sites in human diseases are briefly discussed.

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