scholarly journals ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maxime Boutry ◽  
Peter K. Kim
Keyword(s):  
Lipid Transfer Protein ◽  
Super Resolution ◽  
Lipid Transfer ◽  
Direct Role ◽  
Mitochondrial Division ◽  
Transfer Protein ◽  
Division Site ◽  
Associated Proteins ◽  
Division Process ◽  
Phosphatidylinositol 4

AbstractMitochondrial division is not an autonomous event but involves multiple organelles, including the endoplasmic reticulum (ER) and lysosomes. Whereas the ER drives the constriction of mitochondrial membranes, the role of lysosomes in mitochondrial division is not known. Here, using super-resolution live-cell imaging, we investigate the recruitment of lysosomes to the site of mitochondrial division. We find that the ER recruits lysosomes to the site of division through the interaction of VAMP-associated proteins (VAPs) with the lysosomal lipid transfer protein ORP1L to induce a three-way contact between the ER, lysosome, and the mitochondrion. We also show that ORP1L might transport phosphatidylinositol-4-phosphate (PI(4)P) from lysosomes to mitochondria, as inhibiting its transfer or depleting PI(4)P at the mitochondrial division site impairs fission, demonstrating a direct role for PI(4)P in the division process. Our findings support a model where the ER recruits lysosomes to act in concert at the fission site for the efficient division of mitochondria.

scholarly journals ORP5 regulates PI(4)P on the lipid droplet: Novel players on the monolayer

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Mike F. Renne ◽  
Brooke M. Emerling
Keyword(s):  
Lipid Droplet ◽  
Lipid Composition ◽  
Lipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Contact Sites ◽  
Phosphatidylinositol 4

How the distinct lipid composition of organelles is determined and maintained is still poorly understood. In this issue, Du et al. (2019. J. Cell Biol.https://doi.org/10.1083/jcb.201905162) show that the lipid transfer protein ORP5 functions at ER–LD contact sites, regulating lipid droplet levels of phosphatidylserine and phosphatidylinositol-4-phosphate.

scholarly journals Regulation of secretory transport by protein kinase D–mediated phosphorylation of the ceramide transfer protein

2007 ◽  
Vol 178 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Tim Fugmann ◽  
Angelika Hausser ◽  
Patrik Schöffler ◽  
Simone Schmid ◽  
Klaus Pfizenmaier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lipid Transfer Protein ◽  
Membrane Integrity ◽  
Protein Kinase D ◽  
Lipid Transfer ◽  
Sphingomyelin Synthase ◽  
Transfer Protein ◽  
Secretory Transport ◽  
Phosphatidylinositol 4

Protein kinase D (PKD) has been identified as a crucial regulator of secretory transport at the trans-Golgi network (TGN). Recruitment and activation of PKD at the TGN is mediated by the lipid diacylglycerol, a pool of which is generated by sphingomyelin synthase from ceramide and phosphatidylcholine. The nonvesicular transfer of ceramide from the endoplasmic reticulum to the Golgi complex is mediated by the lipid transfer protein CERT (ceramide transport). In this study, we identify CERT as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT toward its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. We also show that CERT, in turn, is critical for PKD activation and PKD-dependent protein cargo transport to the plasma membrane. Thus, the interdependence of PKD and CERT is key to the maintenance of Golgi membrane integrity and secretory transport.

The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol

2018 ◽  
Vol 87 (1) ◽  
pp. 809-837 ◽  
Author(s):  
Bruno Antonny ◽  
Joëlle Bigay ◽  
Bruno Mesmin
Keyword(s):  
Secretory Pathway ◽  
Lipid Transfer Protein ◽  
Binding Protein ◽  
Asymmetric Distribution ◽  
Lipid Transfer ◽  
Oxysterol Binding Protein ◽  
Transfer Protein ◽  
Lipid Exchange ◽  
Opposite Process ◽  
Phosphatidylinositol 4

To maintain an asymmetric distribution of ions across membranes, protein pumps displace ions against their concentration gradient by using chemical energy. Here, we describe a functionally analogous but topologically opposite process that applies to the lipid transfer protein (LTP) oxysterol-binding protein (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Because of the subsequent hydrolysis of PI(4)P, this counterexchange is irreversible and contributes to the establishment of a cholesterol gradient along organelles of the secretory pathway. The facts that some natural anti-cancer molecules block OSBP and that many viruses hijack the OSBP cycle for the formation of intracellular replication organelles highlight the importance and potency of OSBP-mediated lipid exchange. The architecture of some LTPs is similar to that of OSBP, suggesting that the principles of the OSBP cycle—burning PI(4)P for the vectorial transfer of another lipid—might be general.

scholarly journals The key to the allergenicity of lipid transfer protein (LTP) ligands: A structural characterization

2021 ◽  
pp. 158928
Author(s):  
Zulema Gonzalez-Klein ◽  
Bruno Cuevas-Zuviria ◽  
Andrea Wangorsch ◽  
Guadalupe Hernandez-Ramirez ◽  
Diego Pazos-Castro ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Lipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein

scholarly journals Structural Characterization of Act c 10.0101 and Pun g 1.0101—Allergens from the Non-Specific Lipid Transfer Protein Family

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 256
Author(s):  
Andrea O’Malley ◽  
Swanandi Pote ◽  
Ivana Giangrieco ◽  
Lisa Tuppo ◽  
Anna Gawlicka-Chruszcz ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Lipid Transfer Protein ◽  
Mass Spectrometry Analysis ◽  
Lipid Transfer ◽  
Helical Structures ◽  
Spectrometry Analysis ◽  
X Ray Crystallography ◽  
Transfer Protein ◽  
Specific Lipid

(1) Background: Non-specific lipid transfer proteins (nsLTPs), which belong to the prolamin superfamily, are potent allergens. While the biological role of LTPs is still not well understood, it is known that these proteins bind lipids. Allergen nsLTPs are characterized by significant stability and resistance to digestion. (2) Methods: nsLTPs from gold kiwifruit (Act c 10.0101) and pomegranate (Pun g 1.0101) were isolated from their natural sources and structurally characterized using X-ray crystallography (3) Results: Both proteins crystallized and their crystal structures were determined. The proteins have a very similar overall fold with characteristic compact, mainly α-helical structures. The C-terminal sequence of Act c 10.0101 was updated based on our structural and mass spectrometry analysis. Information on proteins’ sequences and structures was used to estimate the risk of cross-reactive reactions between Act c 10.0101 or Pun g 1.0101 and other allergens from this family of proteins. (4) Conclusions: Structural studies indicate a conformational flexibility of allergens from the nsLTP family and suggest that immunoglobulin E binding to some surface regions of these allergens may depend on ligand binding. Both Act c 10.0101 and Pun g 1.0101 are likely to be involved in cross-reactive reactions involving other proteins from the nsLTP family.

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