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Unlike most other organelles found in multiple copies, the endoplasmic reticulum (ER) is a unique singular organelle within eukaryotic cells. Despite its continuous membrane structure, encompassing more than half of the cellular endomembrane system, the ER is subdivided into specialized sub-compartments, including morphological, membrane contact site (MCS), and de novo organelle biogenesis domains. In this review, we discuss recent emerging evidence indicating that, in response to nutrient stress, cells undergo a reorganization of these sub-compartmental ER domains through two main mechanisms: non-destructive remodeling of morphological ER domains via regulation of MCS and organelle hitchhiking, and destructive remodeling of specialized domains by ER-phagy. We further highlight and propose a critical role of membrane lipid metabolism in this ER remodeling during starvation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Herein we present a FRET-based theranostic macromolecular prodrug (TMP) composed of (a) dendritic polyglycerol (PG) as polymeric nanocarrier, (b) doxorubicin (Dox) linked via a pH-sensitive hydrazone to (c) a tri-functional linker, and (d) an indodicarbocyanine dye (IDCC) attached in close proximity to Dox. The drug fluorescence is quenched via intramolecular FRET until the pH-sensitive hydrazone bond between the TMP and Dox is cleaved at acidic pH. By measuring its fluorescence, we characterized the TMP cleavage kinetics at different pH values in vitro. The intracellular release of Dox from the carrier was monitored in real time in intact cancer cells, giving more insight into the mode of action of a polymer drug conjugate., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Neurotransmission is based on the exocytic release of neurotransmitters from synaptic vesicles (SVs) at nerve terminals and the subsequent retrieval of SV membranes. Evidence from genetic analysis of model organisms, high-resolution imaging, and biochemical studies indicate that, in addition to the well-studied function of exo-endocytic protein networks, membrane lipids and their derivatives play a key role in SV cycling. These include structural lipids such as cholesterol and sphingolipids as well as phosphoinositides (PIs), which interact with select components of the exocytic and endocytic machineries, thereby coupling both limbs of the SV cycle. Here we provide an overview of the function of lipids in SV cycling and discuss potential models of how lipids and lipid-protein interactions may regulate presynaptic function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Although vesicular transport in eukaryotic cells involves a number of different carriers, one common feature is that most of them use small GTPases to direct coat assembly at the donor membrane. COPII coated vesicles bud from the endoplasmic reticulum to selectively export secretory cargo en route to the Golgi complex. Vesicle formation involves the stepwise recruitment of the small GTPase Sar1 and two large heterodimeric complexes Sec23-Sec24 and Sec13-Sec31 to the membrane. A new structural study now provides breathtaking molecular insights into the formation of the Sec23-Sec24-Sar1 pre-budding complex and into COPII coat assembly.

Clathrin-mediated endocytosis is a vesicular transport event involved in the internalization and recycling of receptors participating in signal transduction events and nutrient import as well as in the reformation of synaptic vesicles. Recent studies in vitro and in living cells have provided a number of new insights into the initial steps of clathrin-coated vesicle formation and the membrane factors involved in this process. The unexpected complexity of these interactions at the cytosol-membrane interface suggests that clathrin-coated vesicle assembly is a highly cooperative process occurring under tight regulatory control. In this review, we focus on the role of membrane proteins and lipids in the nucleation of clathrin-coated pits and provide a hypothetical model for the early steps in clathrin-mediated endocytosis.

Although mitochondria and chloroplasts synthesize some of their own proteins, they must import most of them from the cytosol. Import is mediated by molecular chaperones in the cytosol, receptors and channels in the organelle membranes and ATP-driven 'import motors' inside the organelles. Many of these components are now known, allowing informed guesses on how they might work.