ArticleHepatology communications2021
RORα Enhances Lysosomal Acidification and Autophagic Flux in the Hepatocytes.
Article in Hepatology communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Mitochondrial Dysfunction in Metabolic-Syndrome-Related MASLD/MASH: Metabolic Mechanisms and Therapeutic Perspectives.Metabolites · 2026Review
- ATP6V1B2 alleviates hepatic steatosis by promoting lysosomal acidification in hepatocytes.Cell death discovery · 2026Article
- LncRNA Wee1-AS coordinates oxidative fatty acid metabolism through the activation of mitochondrial CDK1/CYCLIN B1.Signal transduction and targeted therapy · 2026Article
- Transient exposure to bisphenol F in early life affects the metabolic health of adults.Exposome · 2026Article
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- Liver diseases: epidemiology, causes, trends and predictions.Signal transduction and targeted therapy · 2025Review
- Mechanisms and therapeutic implications of selective autophagy in nonalcoholic fatty liver disease.Journal of advanced research · 2025Review
- The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis.International journal of molecular sciences · 2024Review
- HERV-K (HML-2) Envelope Protein Induces Mitochondrial Depolarization and Neurotoxicity via Endolysosome Iron Dyshomeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- RORα-GABP-TFAM axis alleviates myosteatosis with fatty atrophy through reinforcement of mitochondrial capacity.Journal of cachexia, sarcopenia and muscle · 2024Article
- The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells.Biomolecules · 2024Article
- Identification and validation of ATP6V1G1-regulated phosphorylated proteins in hepatocellular carcinoma.PloS one · 2024Article
- Nobiletin, a polymethoxylated flavonoid, regulates cell survival via the nuclear receptor RORα in cardiomyocytes.The journal of cardiovascular aging · 2024Article
- Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction.Molecules and cells · 2023Review
- Review
- Nuclear Receptor RORα/γ: Exciting Modulators in Metabolic Syndrome and Related Disorders.Frontiers in nutrition · 2022Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomes are intracellular acidic organelles with catabolic functions that contribute to the activation of autophagy. Although autophagy abnormality is associated with defects in lysosomal acidification during the progression of nonalcoholic fatty liver disease (NAFLD), the mechanisms of control of lysosomal acidification are not well understood at the molecular level. Thus, we aimed to elucidate the role of the orphan nuclear receptor retinoic acid-related orphan receptor α (RORα) in lysosomal acidification and autophagic flux, particularly in nutrition-enriched hepatocytes. First, lysosomal acidity was much lower in the hepatocytes obtained from hepatocyte-specific RORα-deleted (RORα-LKO) mice, whereas the infusion of an adenovirus encoding RORα in wild-type hepatocytes increased lysosomal acidity, as determined by LysoSensor. Second, the lysosomal translocation of the mechanistic target of rapamycin was increased and immature cathepsin D was accumulated in the liver of RORα-LKO mice. Third, the accumulation of LC3-II, p62/sequestosome 1 (SQSTM1), and neighbor of BRCA1 gene 1 (NBR1) was increased in the livers of RORα-LKO mice, indicating an impaired autophagic flux in the livers. Consistently, the number of autolysosomes containing mitochondria and lipid droplets was dramatically reduced in the RORα-deleted hepatocytes. Finally, we found that RORα induced the transcription of genes involved in lysosomal function, such as Atp6v1g1, a vacuolar H
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