Membrane dynamics and organelle biogenesis—lipid pipelines and vesicular carriers

Stefan, Christopher J.; Trimble, William S.; Grinstein, Sergio; Drin, Guillaume; Reinisch, Karin M; Camilli, Pietro De; Cohen, Sarah; Valm, Alex M.; Lippincott‐Schwartz, Jennifer; Levine, Tim P.; Iaea, David B.; Maxfield, Frederick R.; Futter, Clare E.; Eden, Emily R.; Judith, Delphine; Vliet, Alexander R. van; Agostinis, Patrizia; Tooze, Sharon A.; Sugiura, Ayumu; McBride, Heidi M.

doi:10.1186/s12915-017-0432-0

Cited by 69 publications

(49 citation statements)

References 180 publications

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“…In 2015, the Bao-Liang Song research group demonstrated that cholesterol transport is abnormal in ALD fibroblasts and in the Abcd1 mouse model for ALD as well as in other peroxisomal disorders. Low-density lipoprotein (LDL)-derived cholesterol was transported from the lysosome to the peroxisome in a manner that depended upon lysosomal synaptotagmin VII binding to the peroxisomal lipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P 2 ] on the peroxisomal membrane (Chu et al, 2015;Hu et al, 2018;Islinger, Voelkl, Fahimi, & Schrader, 2018;Jin, Strunk, & Weisman, 2015;Luo, Jiang, Yang, & Song, 2018;Luo, Liao, Xiao, & Song, 2017;Stefan et al, 2017). While these findings were initially called into question by van Veldhoven et al in a letter to the editor (van Veldhoven, Baes, & Fransen, 2015), correctly identifying an error in Chu et al's method, a recent follow-up publication (Xiao et al, 2019) validates the initial Chu et al (2015) findings.…”

Section: Cholesterol Transport In Aldmentioning

confidence: 99%

X‐linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

Turk

Theda

Fatemi

et al. 2020

Intl J of Devlp Neuroscience

128

113

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Adrenoleukodystrophy (ALD) is a rare X‐linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell‐ and tissue‐specific roles of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials and the advent of newborn screening in the USA. In ALD, very long‐chain fatty acid (VLCFA) chain length‐dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety‐specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.

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Section: Cholesterol Transport In Aldmentioning

confidence: 99%

X‐linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

Turk

Theda

Fatemi

et al. 2020

Intl J of Devlp Neuroscience

128

113

View full text Add to dashboard Cite

show abstract

“…Cellular cholesterol homeostasis depends critically on sterol flux through LE/LYSs, but the pathways and molecular mechanisms of sterol trafficking between these organelles and other membranes are poorly defined 51,52 . In Niemann-Pick type C2 disease, cholesterol and other lipids build up due to lack of a small sterol-transfer protein, NPC2, in the lumen of LE/LYSs.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cholesterol export from endo-lysosomes by Niemann Pick C2 protein using combined fluorescence and X-ray microscopy

Dupont

Mlv

et al. 2018

Preprint

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The Niemann-Pick C2 protein (NPC2) is a sterol transfer protein in late endosomes and lysosomes (LE/LYSs). How its capacity to transport cholesterol between membranes is linked to endolysosomal membrane trafficking is not known. Using quantitative fluorescence imaging combined with soft X-ray tomography (SXT); we show that NPC2 mediated sterol efflux is accompanied by large changes in distribution, size and ultrastructure of endocytic organelles. We observed clearance of intra-luminal lipid deposits, a decrease in number of autophagosomes, formation of membrane contact sites (MCSs) to the endoplasmic reticulum and extensive tubulation of LE/LYSs in threedimensional SXT reconstructions of NPC2 treated human fibroblasts. The cells could recycle the cholesterol analog dehydroergosterol (DHE) from LE/LYSs slowly also in the absence of NPC2 protein but internalized NPC2 synchronized and accelerated this process significantly. Most fluorescent NPC2 was retained in LE/LYSs while DHE was selectively removed from these organelles, at least partially by non-vesicular exchange with other membranes. During sterol efflux LE/LYSs were reallocated to the cell periphery, where they could fuse with newly formed endosomes. Surface shedding of micro-vesicles was found, suggesting a pathway for cellular sterol release. We conclude that NPC2 mediated sterol efflux from LE/LYSs controls membrane traffic through the endo-lysosomal pathway.

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“…The best characterized machinery of this type is the lipid transfer by Osh4 transporting sterols from the ER to the trans ‐Golgi . Not only sterols, but also glycerophospholipids are actively transported by non‐vesicular traffic . Here, the counterflow and turnover of PI4P serves a dual role in energizing lipid transport and marking organelle identity.…”

Section: Compendium Of Physicochemical Membrane Propertiesmentioning

confidence: 99%

An Emerging Group of Membrane Property Sensors Controls the Physical State of Organellar Membranes to Maintain Their Identity

et al. 2018

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The biological membranes of eukaryotic cells harbor sensitive surveillance systems to establish, sense, and maintain characteristic physicochemical properties that ultimately define organelle identity. They are fundamentally important for membrane homeostasis and play active roles in cellular signaling, protein sorting, and the formation of vesicular carriers. Here, we compare the molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of fatty acid desaturation and the response to unfolded proteins and lipid bilayer stress in order to identify their commonalities and specializations. We will speculate on the cellular significance of membrane property sensors in other organelles and discuss their putative mechanisms. Based on these findings, we propose membrane property sensors as an emerging class of proteins with wide implications for organelle communication and function.

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Membrane dynamics and organelle biogenesis—lipid pipelines and vesicular carriers

Cited by 69 publications

References 180 publications

X‐linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

X‐linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

Analysis of cholesterol export from endo-lysosomes by Niemann Pick C2 protein using combined fluorescence and X-ray microscopy

An Emerging Group of Membrane Property Sensors Controls the Physical State of Organellar Membranes to Maintain Their Identity

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