Abstract

Phospholipids are synthesized at the endoplasmic reticulum (ER), the largest membrane bound organelle that forms membrane contact sites (MCS) with almost every other organelle. MCS are locations at which the membranees of two organelles are closely positioned to provide a microenvironment where proteins in one membrane can interact with the opposite membrane. Thus, MCS provide an ideal location at which lipid transfer proteins (LTPs) can achieve the efficient transfer of individual classes of lipids from the ER to other organelles via non-vesicular transport. Here we provide an overview of emerging findings on the localization and biochemical activity of LTPs at MCS between the ER and other cellular membranes. The localization of LTPs at MCS offers an elegant cell biological solution to tune local lipid composition to ongoing cell physiology.

Highlights

  • The endoplasmic reticulum (ER) is the main site of phospholipid synthesis and provides lipids to other membrane compartments by vesicular and non-vesicular transport

  • Depletion of ORP5/ORP8 leads to altered mitochondrial morphology and function. These findings indicate that PS production and transport at the ER–mitochondrial membrane contact sites (MCS) is required to support mitochondrial function

  • General conclusions lipid transfer proteins (LTPs) were initially identified as soluble single domain proteins that could transfer lipids between membrane compartments in vitro

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Summary

Introduction

The endoplasmic reticulum (ER) is the main site of phospholipid synthesis and provides lipids to other membrane compartments by vesicular and non-vesicular transport. The ER is an elaborate network of membranes making contact with most organelles including mitochondria, plasma membranes (PM), endosomes, lysosomes, peroxisomes, Golgi apparatus, lipid droplets and autophagosomes (Figure 1) These areas of close contact, referred to as membrane contact sites (MCS), are formed by transient associations or can be stably present depending on cell type and context. The ER is the main site of lipid synthesis and makes contact with many organelles At these membrane contact sites, lipid transfer proteins from different families defined by the presence of specific domains such as the ORD, START, Acyl-CoA, SMP and PITP domains mediate lipid exchange. RdgBa mutants show depletion of PM PI(4,5)P2 in the resting state and reduced rates of PI(4,5)P2 resynthesis www.sciencedirect.com during PLC activation [9,10] These biochemical defects affect photoreceptor function resulting in reduced responses to light and retinal degeneration.

54 Membrane trafficking
36. Michell RH

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