Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 21, 2023

Abstract Abnormal distribution of cellular cholesterol is associated with numerous diseases, including cardiovascular and neurodegenerative diseases. Regulated transport critical for maintaining its proper in the cell, yet underlying mechanisms remain unclear. Here, we show that lipid transfer proteins, namely ORP9, OSBP, GRAMD1s/Asters (GRAMD1a/GRAMD1b/GRAMD1c), control non-vesicular at points contact between ER trans-Golgi network (TGN), thereby distribution. ORP9 localizes to TGN via interaction tandem α-helices ORP10/ORP11. extracts PI4P from prevent overaccumulation suppresses OSBP-mediated PI4P-driven Golgi. By contrast, GRAMD1s excess Golgi ER, preventing build-up. Cells lacking exhibit accumulation Golgi, which further enhanced by additional depletion major plasma membrane. This accompanied chronic activation SREBP-2 signalling pathway. Our findings reveal importance regulated ER-Golgi contacts homeostasis.

Язык: Английский

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Lipid scrambling is a general feature of protein insertases

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 1, 2023

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow ER membranes derived from it grow. Lipid equilibration is facilitated by integral proteins called "scramblases". These feature a hydrophilic groove allowing polar heads lipids traverse hydrophobic interior, similar credit-card moving through reader. Nevertheless, despite their fundamental role expansion dynamics, identity most scramblases has remained elusive. Here, combining biochemical reconstitution molecular dynamics simulations, we show that lipid scrambling general protein insertases, which insert polypeptide chains into organelles disconnected vesicle trafficking. Our data indicate occurs same channel insertion takes place, abolished presence nascent chains. We propose insertases could have so-far overlooked as scramblases.

Язык: Английский

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Utilization of n-alkane and roles of lipid transfer proteins in Yarrowia lipolytica

World Journal of Microbiology and Biotechnology, Год журнала: 2023, Номер 39(4)

Опубликована: Фев. 14, 2023

Abstract Yarrowia lipolytica , a dimorphic yeast belonging to the Ascomycota, has potent abilities utilize hydrophobic compounds, such as n -alkanes and fatty acids, carbon energy sources. can synthesize accumulate large amounts of lipids, making it promising host produce various lipids convert useful compounds. For advanced use Y. in these applications, is necessary understand metabolism compounds this underlying molecular mechanisms. In review, current knowledge on -alkane how regulated summarized. Furthermore, recent studies revealed that lipid transfer proteins are involved utilization regulation cell morphology response -alkanes. This review discusses roles membrane processes .

Язык: Английский

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Membrane specificity of the human cholesterol transfer protein STARD4

Journal of Molecular Biology, Год журнала: 2024, Номер 436(11), С. 168572 - 168572

Опубликована: Апрель 12, 2024

STARD4 regulates cholesterol homeostasis by transferring between the plasma membrane and endoplasmic reticulum. The structure features a helix-grip fold surrounding large hydrophobic cavity holding sterol. Its access is controlled gate formed Ω1 Ω4 loops C-terminal α-helix. Little known about mechanisms which binds to membranes extracts/releases cholesterol. All available structures of are without bound sterol display same closed conformation gate. transfer activity mouse enhanced in presence anionic lipids, particular phosphatidylinositol biphosphates (PIP2) for two binding sites were proposed on surface. Yet only one these conserved human STARD4. We here report results liposome microarray-based assay microseconds-long molecular dynamics simulations with complex lipid bilayers mimicking composition donor acceptor membranes. show that apo form sensitive PIP2 through specific sites, was not identified novel conformations holo-STARD4: yet-unobserved close an open shedding light opening/closure mechanism needed uptake/release. Overall, modulation membrane-binding composition, cargo supports capacity achieve directed organelle

Язык: Английский

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The Vps13-like protein BLTP2 is pro-survival and regulates phosphatidylethanolamine levels in the plasma membrane to maintain its fluidity and function

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 5, 2024

Lipid transport proteins (LTPs) facilitate nonvesicular lipid exchange between cellular compartments and have critical roles in homeostasis

Язык: Английский

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