ArticleThe Journal of cell biology2022
ORP5 and ORP8 orchestrate lipid droplet biogenesis and maintenance at ER-mitochondria contact sites.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 95 citations in OpenAlex.
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- Tripartite ER-mitochondria-lipid droplets contact sites control adipocyte metabolic flexibility.The EMBO journal · 2026Article
- Article
- The interplay of lipid droplets, mitochondria, and ER in governing hepatic lipid metabolism.Current opinion in cell biology · 2026Review
- Quantitative FRET FLIM imaging reveals multiple interactions between proteins of the ESYT, ORP, and VAP families at the endoplasmic reticulum membrane.The Journal of biological chemistry · 2026Article
- Functional analysis of LIPID TRANSFER PROTEIN 6 (LTP6) in pennycress and Arabidopsis reveals divergent roles in oil storage and seed coat development.The Plant journal : for cell and molecular biology · 2026Article
- Lipid traffic: an enigmatic alliance between ORPs and a TMEM16-like protein at membrane contact sites.Biochemical Society transactions · 2026Review
- Heterogeneity, dynamics and organelle interactions of lipid droplets.Nature reviews. Molecular cell biology · 2026Review
- Mitochondria-ER contact sites (MERCS) in the cell cycle: molecular architecture and functional remodeling across cellular states.BMC biology · 2026Review
- L-type calcium channel-mediated lipid metabolic reprogramming in gastric adenocarcinoma progression.Translational oncology · 2026Article
- Lipid droplet-associated proteins: Roles in cardiovascular diseases.Journal of lipid research · 2026Review
- Alzheimer's disease: disrupted communication between the endoplasmic reticulum and mitochondria.Journal of neurology · 2026Review
- OSBPL2 deficiency alleviates diet-induced MASLD by reducing ACSL4-mediated ferroptosis.iScience · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression.Cell · 2026Article
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- The PVAT-MAMs Axis in Atherosclerosis: A Hypothesis-Driven Cross-Scale Conceptual Framework.International journal of molecular sciences · 2026Review
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- GLP-1 receptor and Mitochondria-ER Contact Sites: an emerging mechanism of metabolic regulation.Frontiers in physiology · 2026Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Lipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the endoplasmic reticulum (ER). The ER protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at mitochondria-associated ER membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulates seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis and maturation at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at the membrane contact sites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.