Aster-B–dependent estradiol synthesis protects female mice from diet-induced obesity DOI Creative Commons
Xiao Xu, John P. Kennelly, An‐Chieh Feng

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(4)

Опубликована: Янв. 4, 2024

Aster proteins mediate the nonvesicular transport of cholesterol from plasma membrane (PM) to endoplasmic reticulum (ER). However, importance sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss Aster-B leads diet-induced obesity insulin resistance female but not male mice, this sex difference abolished by ovariectomy. We further demonstrate deficiency impairs PM ER ovaries vivo, leading hypogonadism reduced estradiol synthesis. Female Aster-B-deficient mice exhibit locomotor activity energy expenditure, consistent with established effects estrogens on systemic metabolism. Administration exogenous ameliorates phenotype mice. These findings highlight key role Aster-B-dependent regulating production protecting females obesity.

Язык: Английский

Skin rejuvenation and photoaging protection using adipose‐derived stem cell extracellular vesicles loaded with exogenous cargos DOI Creative Commons

Diem D. N. Nguyen,

Diem My Vu,

Nhan Thanh Vo

и другие.

Skin Research and Technology, Год журнала: 2024, Номер 30(2)

Опубликована: Янв. 26, 2024

Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial standardize cost-effective methods produce highly pure ASC-sEVs.

Язык: Английский

Процитировано

10
Cholesterol trafficking to the ER leads to the activation of CaMKII/JNK/NLRP3 and promotes atherosclerosis DOI Creative Commons
Mustafa Yalcınkaya, Wenli Liu, Tong Xiao

и другие.

Journal of Lipid Research, Год журнала: 2024, Номер 65(4), С. 100534 - 100534

Опубликована: Март 23, 2024

The deposition of cholesterol-rich lipoproteins in the arterial wall triggers macrophage inflammatory responses, which promote atherosclerosis. NLRP3 inflammasome aggravates atherosclerosis; however, cellular mechanisms connecting cholesterol accumulation to activation are poorly understood. We investigated loaded macrophages and atherosclerosis-prone Ldlr-/- mice with defects efflux. found that treated modified LDL or crystals, defective efflux promoting transporters ABCA1 ABCG1, leads inflammasomes as a result increased trafficking from plasma membrane ER, via Aster-B. In turn, ER activates inositol triphosphate-3 receptor, CaMKII/JNK induces deubiquitylation by BRCC3. An inhibitor deficiency Abro1, an essential scaffolding protein BRCC3-containing cytosolic complex, suppressed activation, neutrophil extracellular trap formation (NETosis) atherosclerosis vivo. These results identify link between deubiquitylation,

Язык: Английский

Процитировано

10
Lipids and membrane-associated proteins in autophagy DOI Creative Commons
Linsen Li, Mindan Tong, Yuhui Fu

и другие.

Protein & Cell, Год журнала: 2020, Номер 12(7), С. 520 - 544

Опубликована: Ноя. 5, 2020

Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. a membrane driven process tightly regulated by membrane-associated proteins. Here, we summarized lipid composition, proteins relevant autophagy from spatiotemporal perspective. In particular, focused on three important remodeling processes in autophagy, transfer phagophore elongation, scission closure, autophagosome-lysosome fusion. We discussed significance discoveries this field possible avenues follow future studies. Finally, biochemical techniques assays used study properties, with discussion their applications autophagy.

Язык: Английский

Процитировано

68
Aster Proteins Regulate the Accessible Cholesterol Pool in the Plasma Membrane DOI
Alessandra Ferrari, Cuiwen He, John P. Kennelly

и другие.

Molecular and Cellular Biology, Год журнала: 2020, Номер 40(19)

Опубликована: Июль 28, 2020

Recent studies have demonstrated the existence of a discrete pool cholesterol in plasma membranes (PM) mammalian cells—referred to as accessible pool—that can be detected by binding modified versions bacterial cytolysins (e.g., anthrolysin O). When amount PM exceeds threshold level, excess moves endoplasmic reticulum (ER), where it regulates SREBP2 pathway and undergoes esterification. We reported previously that Aster/Gramd1 family sterol transporters mediates nonvesicular movement from ER multiple cell types. Here, we investigated cholesterol-loaded fibroblasts with knockdown Aster-A mouse macrophages Aster-B Aster-A/B-deficient mice. Nanoscale secondary ion mass spectrometry (NanoSIMS) analyses revealed expansion cells lacking Aster expression. The increased was accompanied reduced ER, evidenced expression SREBP2-regulated genes. Cosedimentation experiments liposomes GRAM domain binds concentration-dependent manner is facilitated presence phosphatidylserine. These Aster-mediated transport controls levels PM, well activity SREBP pathway.

Язык: Английский

Процитировано

57
Cholesterol metabolism: from lipidomics to immunology DOI Creative Commons
William J. Griffiths, Yuqin Wang

Journal of Lipid Research, Год журнала: 2021, Номер 63(2), С. 100165 - 100165

Опубликована: Дек. 22, 2021

Oxysterols, the oxidized forms of cholesterol or its precursors, are formed in first steps metabolism. Oxysterols have interested chemists, biologists, and physicians for many decades, but their exact biological relevance vivo, other than as intermediates bile acid biosynthesis, has long been debated. However, quarter this century, a role side-chain oxysterols C-7 metabolites convincingly established immune system. 25-Hydroxycholesterol shown to be synthesized by macrophages response activation Toll-like receptors offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol act chemoattractant lymphocytes expressing G protein-coupled receptor Epstein-Barr virus-induced gene 2 important coordinating action B cells, T dendritic cells secondary lymphoid tissue. There is growing body evidence that not only these two also isomers importance proper function Here, we review recent findings related roles immunology.

Язык: Английский

Процитировано

49
Patched 1 reduces the accessibility of cholesterol in the outer leaflet of membranes DOI Creative Commons
Maia Kinnebrew, Giovanni Luchetti, Ria Sircar

и другие.

eLife, Год журнала: 2021, Номер 10

Опубликована: Окт. 26, 2021

A long-standing mystery in vertebrate Hedgehog signaling is how Patched 1 (PTCH1), the receptor for ligands, inhibits activity of Smoothened, protein that transmits signal across membrane. We previously proposed (Kinnebrew et al., 2019) PTCH1 Smoothened by depleting accessible cholesterol from ciliary Using a new imaging-based assay to directly measure transport PTCH1, we find depletes outer leaflet plasma This terminated binding ligands or dissipation transmembrane potassium gradient. These results point unexpected model moves inner membrane exchange ion export opposite direction. Our study provides plausible solution SMO changing organization membranes and establishes general framework studying proteins change accessibility regulate membrane-dependent processes cells.

Язык: Английский

Процитировано

45
A sublethal ATP11A mutation associated with neurological deterioration causes aberrant phosphatidylcholine flipping in plasma membranes DOI Open Access
Katsumori Segawa, Atsuo Kikuchi, Tomoyasu Noji

и другие.

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(18)

Опубликована: Авг. 17, 2021

ATP11A translocates phosphatidylserine (PtdSer), but not phosphatidylcholine (PtdCho), from the outer to inner leaflet of plasma membranes, thereby maintaining asymmetric distribution PtdSer. Here, we detected a de novo heterozygous point mutation in patient with developmental delays and neurological deterioration. Mice carrying corresponding died perinatally disorders. This caused an amino acid substitution (Q84E) first transmembrane segment ATP11A, mutant flipped PtdCho. Molecular dynamics simulations revealed that allowed PtdCho binding at substrate entry site. Aberrant flipping markedly decreased concentration whereas sphingomyelin (SM) concentrations increased. change phospholipids altered cell characteristics, including growth, cholesterol homeostasis, sensitivity sphingomyelinase. Matrix-assisted laser desorption ionization–imaging mass spectrometry (MALDI-IMS) showed marked increase SM levels brains Q84E-knockin mouse embryos. These results provide insights into physiological importance specificity membrane flippases for proper SM.

Язык: Английский

Процитировано

43
GPCRs in Intracellular Compartments: New Targets for Drug Discovery DOI Creative Commons
Irene Fasciani, Marco Carli, Francesco Petragnano

и другие.

Biomolecules, Год журнала: 2022, Номер 12(10), С. 1343 - 1343

Опубликована: Сен. 22, 2022

The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional differences between cells. G protein-coupled receptors (GPCRs) are the largest class cell surface receptors, and their signal transduction traditionally viewed as a chain events initiated from plasma membrane. Furthermore, intracellular trafficking, internalization, recycling were considered only regulate receptor desensitization expression. On contrary, accumulating data strongly suggest GPCRs also compartments. localize in membranes endosomes, nucleus, Golgi endoplasmic reticulum apparatuses, mitochondria, division Importantly, these sites they have shown orchestrate multiple signals different pathways. In this review, we summarize current knowledge fascinating phenomenon, explaining how reach sites, stimulated endogenous ligands, potential physiological/pathophysiological roles. Finally, illustrate several mechanisms involved modulation compartmentalized GPCR signaling drugs ligands. Understanding compartmentalization regulated will provide unique opportunity develop novel pharmaceutical approaches target potentially lead way towards new therapeutic approaches.

Язык: Английский

Процитировано

36
Interplay between Asters/GRAMD1s and phosphatidylserine in intermembrane transport of LDL cholesterol DOI Creative Commons
Michael N. Trinh, Michael S. Brown, Joachim Seemann

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(2)

Опубликована: Янв. 6, 2022

Significance Cholesterol constitutes 50% of lipids in the plasma membrane (PM) animal cells. Sensors endoplasmic reticulum (ER) maintain this level by adjusting cholesterol uptake, synthesis, and storage. Uptake is mediated LDL receptors, which deliver cholesterol-carrying to lysosomes from moves PM then ER. We report PM-to-ER transport requires cholesterol-binding Aster proteins anchored ER phosphatidylserine embedded PM. Asters are known bind phosphatidylserine, accounts for part requirement. However, current data suggest an additional requirement independent Asters. These advance our knowledge homeostasis, a control mechanism essential cell growth survival.

Язык: Английский

Процитировано

33
Low-Density Lipoprotein Internalization, Degradation and Receptor Recycling Along Membrane Contact Sites DOI Creative Commons
Mohammad Majharul Islam, Iryna Hlushchenko, Simon G. Pfisterer

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Янв. 24, 2022

Low-density lipoprotein (LDL) internalization, degradation, and receptor recycling is a fundamental process underlying hypercholesterolemia, high blood cholesterol concentration, affecting more than 40% of the western population. Membrane contact sites influence endosomal dynamics, plasma membrane lipid composition, cellular distribution. However, if we focus on LDL-related trafficking events mostly discuss them in an isolated fashion, without context. It our goal to change this perspective highlight that all steps from LDL internalization are likely associated with dynamic which endosomes engage endoplasmic reticulum other organelles.

Язык: Английский

Процитировано

33