ArticleProceedings of the National Academy of Sciences of the United States of America2020
Direct lysosome-based autophagy of lipid droplets in hepatocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 229 citations in OpenAlex.
- Bovine viral diarrhea virus (BVDV) relies on cellular lipid droplet biogenesis and lipolysis to provide energy for viral replication.Veterinary research · 2026Article
- GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease: mechanistic networks and translational implications: a review.Journal of endocrinological investigation · 2026Review
- Effects of a Chemically Characterised Multi-Component Nutraceutical Formulation on Intestinal, Hepatic and Skeletal Muscle Responses in an In Vitro Gut-Liver-Muscle Model.International journal of molecular sciences · 2026Article
- Mito-TEMPO improves survival rates inScience advances · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Article
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Cell surface liposome binding (CLiB) allows lipid-binding probe engineering via high-throughput screening.Nature cell biology · 2026Article
- ARF-like GTPase 8B orchestrates lipophagy and exocytosis to drive single-stranded RNA virus replication.Journal of translational medicine · 2026Article
- Lysosomal lipid metabolism promotes tumor cell invasion through local energetics and membrane lipid remodeling.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneity, dynamics and organelle interactions of lipid droplets.Nature reviews. Molecular cell biology · 2026Review
- A PI(3,5)PNature communications · 2026Article
- Seipin-defined ER sites undergo distinct enrichment of factors for the biogenesis of sterol ester rich lipid droplets.iScience · 2026Article
- Novel Pharmacological and Nanotechnology-Based Therapeutic Strategies for MASLD.Pharmaceutics · 2026Review
- In vivo visualization of lipophagy dynamics using the tfLiveDrop reporter mice.Journal of lipid research · 2026Article
- Hepatocyte-Specific Deletion of Betaine-Homocysteine Methyltransferase Disrupts Methionine Metabolism and Promotes the Spontaneous Development of Hepatic Steatosis.Biomolecules · 2026Article
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- β-Sitosterol ameliorates metabolic dysfunction-associated steatohepatitis by targeting the RAC1/mTOR/TFEB axis thus activating lipophagy-lysosomal pathway.Acta pharmacologica Sinica · 2026Article
75 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form of this process (macrolipophagy) results in the engulfment of LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether this is an exclusive autophagic mechanism used by hepatocytes to catabolize LDs is unclear. It is also unknown whether lysosomes alone might be sufficient to mediate LD turnover in the absence of an autophagosomal intermediate. We performed live-cell microscopy of hepatocytes to monitor the dynamic interactions between lysosomes and LDs in real-time. We additionally used a fluorescent variant of the LD-specific protein (PLIN2) that exhibits altered fluorescence in response to LD interactions with the lysosome. We find that mammalian lysosomes and LDs undergo interactions during which proteins and lipids can be transferred from LDs directly into lysosomes. Electron microscopy (EM) of primary hepatocytes or hepatocyte-derived cell lines supports the existence of these interactions. It reveals a dramatic process whereby the lipid contents of the LD can be "extruded" directly into the lysosomal lumen under nutrient-limited conditions. Significantly, these interactions are not affected by perturbations to crucial components of the canonical macroautophagy machinery and can occur in the absence of double-membrane lipoautophagosomes. These findings implicate the existence of an autophagic mechanism used by mammalian cells for the direct transfer of LD components into the lysosome for breakdown. This process further emphasizes the critical role of lysosomes in hepatic LD catabolism and provides insights into the mechanisms underlying lipid homeostasis in the liver.
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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.