Non-vesicular lipid trafficking at the endoplasmic reticulum–mitochondria interface

2018 ◽  
Vol 46 (2) ◽  
pp. 437-452 ◽  
Author(s):  
Francesca Giordano
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transport Pathways ◽  
Lipid Trafficking ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Mitochondria are highly dynamic organelles involved in various cellular processes such as energy production, regulation of calcium homeostasis, lipid trafficking, and apoptosis. To fulfill all these functions and preserve their morphology and dynamic behavior, mitochondria need to maintain a defined protein and lipid composition in both their membranes. The maintenance of mitochondrial membrane identity requires a selective and regulated transport of specific lipids from/to the endoplasmic reticulum (ER) and across the mitochondria outer and inner membranes. Since they are not integrated in the classical vesicular trafficking routes, mitochondria exchange lipids with the ER at sites of close apposition called membrane contact sites. Deregulation of such transport activities results in several pathologies including cancer and neurodegenerative disorders. However, we are just starting to understand the function of ER–mitochondria contact sites in lipid transport, what are the proteins involved and how they are regulated. In this review, we summarize recent insights into lipid transport pathways at the ER–mitochondria interface and discuss the implication of recently identified lipid transfer proteins in these processes.

scholarly journals ORP5 AND ORP8 ORCHESTRATE LIPID DROPLET BIOGENESIS AND MAINTENANCE AT ER-MITOCHONDRIA CONTACT SITES

2021 ◽  
Author(s):  
Valentin Guyard ◽  
Vera F Monteiro-Cardoso ◽  
Mohyeddine Omrane ◽  
Cecile Sauvanet ◽  
Audrey Houcine ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Phosphatidic Acid ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Nucleation And Growth ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Lipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the Endoplasmic Reticulum (ER). The ER-protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at Mitochondria-Associated ER Membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulate seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for the ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at membrane contact sites.

scholarly journals The Hob Proteins: Putative, Novel Lipid Transfer Proteins at ER-PM Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110523
Author(s):  
Sarah D. Neuman ◽  
Amy T. Cavanagh ◽  
Arash Bashirullah
Keyword(s):  
Structural Models ◽  
Model Systems ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Bona Fide ◽  
Membrane Contact ◽  
Mutant Cells ◽  
Critical Process

Nonvesicular transfer of lipids at membrane contact sites (MCS) has recently emerged as a critical process for cellular function. Lipid transfer proteins (LTPs) mediate this unique transport mechanism, and although several LTPs are known, the cellular complement of these proteins continues to expand. Our recent work has revealed the highly conserved but poorly characterized Hobbit/Hob proteins as novel, putative LTPs at endoplasmic reticulum-plasma membrane (ER-PM) contact sites. Using both S. cerevisiae and D. melanogaster model systems, we demonstrated that the Hob proteins localize to ER-PM contact sites via an N-terminal ER membrane anchor and conserved C-terminal sequences. These conserved C-terminal sequences bind to phosphoinositides (PIPs), and the distribution of PIPs is disrupted in hobbit mutant cells. Recently released structural models of the Hob proteins exhibit remarkable similarity to other bona fide LTPs, like VPS13A and ATG2, that function at MCS. Hobbit is required for viability in Drosophila, suggesting that the Hob proteins are essential genes that may mediate lipid transfer at MCS.

scholarly journals The endoplasmic reticulum-mitochondria encounter structure: coordinating lipid metabolism across membranes

2020 ◽  
Vol 401 (6-7) ◽  
pp. 811-820 ◽  
Author(s):  
Benoît Kornmann
Keyword(s):  
Endoplasmic Reticulum ◽  
Bacterial Symbiont ◽  
Exact Role ◽  
Intracellular Lipid ◽  
Lipid Trafficking ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Tethering ◽  
Membrane Contact ◽  
Insight Into

AbstractEndosymbiosis, the beginning of a collaboration between an archaeon and a bacterium and a founding step in the evolution of eukaryotes, owes its success to the establishment of communication routes between the host and the symbiont to allow the exchange of metabolites. As far as lipids are concerned, it is the host that has learnt the symbiont’s language, as eukaryote lipids appear to have been borrowed from the bacterial symbiont. Mitochondria exchange lipids with the rest of the cell at membrane contact sites. In fungi, the endoplasmic reticulum-mitochondria encounter structure (ERMES) is one of the best understood membrane tethering complexes. Its discovery has yielded crucial insight into the mechanisms of intracellular lipid trafficking. Despite a wealth of data, our understanding of ERMES formation and its exact role(s) remains incomplete. Here, I endeavour to summarise our knowledge on the ERMES complex and to identify lingering gaps.

scholarly journals Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. eaaz7714 ◽  
Author(s):  
Justyna Sawa-Makarska ◽  
Verena Baumann ◽  
Nicolas Coudevylle ◽  
Sören von Bülow ◽  
Veronika Nogellova ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
De Novo ◽  
Lipid Transfer ◽  
Related Protein ◽  
Membrane Formation ◽  
Selective Autophagy ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Phosphatidylinositol 3

Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)–containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12–Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum.

scholarly journals Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing?

2016 ◽  
Vol 44 (2) ◽  
pp. 517-527 ◽  
Author(s):  
Louise H. Wong ◽  
Tim P. Levine
Keyword(s):  
Lipid Binding ◽  
Lipid Transfer ◽  
Transmembrane Helices ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Multiple Contacts ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Lipid Binding Proteins

Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices so that they cannot diffuse through the cytosol to deliver lipids. If such proteins target membrane contact sites they may be major players in lipid metabolism. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices anchoring them in the endoplasmic reticulum (ER), making them interesting subjects for study in relation to sterol metabolism. They target a variety of membrane contact sites, including newly described contacts between organelles that were already known to make contact by other means. Lam1–4p target punctate ER–plasma membrane contacts. Lam5p and Lam6p target multiple contacts including a new category: vacuolar non-NVJ cytoplasmic ER (VancE) contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that established the importance of membrane anchored proteins for lipid traffic. However, the question remaining to be solved is the most difficult of all: are LAMs transporters, or alternately are they regulators that affect traffic more indirectly?

Chloroplast lipid synthesis and lipid trafficking through ER–plastid membrane contact sites

2012 ◽  
Vol 40 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Zhen Wang ◽  
Christoph Benning
Keyword(s):  
Fatty Acids ◽  
Current Knowledge ◽  
Lipid Transfer ◽  
Photosynthetic Membrane ◽  
Lipid Trafficking ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Envelope Membranes ◽  
Thylakoid Lipids

Plant chloroplasts contain an intricate photosynthetic membrane system, the thylakoids, and are surrounded by two envelope membranes at which thylakoid lipids are assembled. The glycoglycerolipids mono- and digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol as well as phosphatidylglycerol, are present in thylakoid membranes, giving them a unique composition. Fatty acids are synthesized in the chloroplast and are either directly assembled into thylakoid lipids at the envelope membranes or exported to the ER (endoplasmic reticulum) for extraplastidic lipid assembly. A fraction of lipid precursors is reimported into the chloroplast for the synthesis of thylakoid lipids. Thus polar lipid assembly in plants requires tight co-ordination between the chloroplast and the ER and necessitates inter-organelle lipid trafficking. In the present paper, we discuss the current knowledge of the export of fatty acids from the chloroplast and the import of chloroplast lipid precursors assembled at the ER. Direct membrane contact sites between the ER and the chloroplast outer envelopes are discussed as possible conduits for lipid transfer.

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 Transport Pathways That Contribute to the Cellular Distribution of Phosphatidylserine

2021 ◽  
Vol 9 ◽  
Author(s):  
Guillaume Lenoir ◽  
Juan Martín D’Ambrosio ◽  
Thibaud Dieudonné ◽  
Alenka Čopič
Keyword(s):  
Structural Data ◽  
Cellular Distribution ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transport Pathways ◽  
Flip Flop ◽  
Membrane Contact Sites ◽  
Passive Flow ◽  
Combined Action ◽  
Membrane Contact

Phosphatidylserine (PS) is a negatively charged phospholipid that displays a highly uneven distribution within cellular membranes, essential for establishment of cell polarity and other processes. In this review, we discuss how combined action of PS biosynthesis enzymes in the endoplasmic reticulum (ER), lipid transfer proteins (LTPs) acting within membrane contact sites (MCS) between the ER and other compartments, and lipid flippases and scramblases that mediate PS flip-flop between membrane leaflets controls the cellular distribution of PS. Enrichment of PS in specific compartments, in particular in the cytosolic leaflet of the plasma membrane (PM), requires input of energy, which can be supplied in the form of ATP or by phosphoinositides. Conversely, coupling between PS synthesis or degradation, PS flip-flop and PS transfer may enable PS transfer by passive flow. Such scenario is best documented by recent work on the formation of autophagosomes. The existence of lateral PS nanodomains, which is well-documented in the case of the PM and postulated for other compartments, can change the steepness or direction of PS gradients between compartments. Improvements in cellular imaging of lipids and membranes, lipidomic analysis of complex cellular samples, reconstitution of cellular lipid transport reactions and high-resolution structural data have greatly increased our understanding of cellular PS homeostasis. Our review also highlights how budding yeast has been instrumental for our understanding of the organization and transport of PS in cells.

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