ArticleThe Journal of biological chemistry2009
Peroxisome deficiency causes a complex phenotype because of hepatic SREBP/Insig dysregulation associated with endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- Dysregulated lipid metabolism and hypomyelination in postnatal peroxisome-deficientFrontiers in molecular neuroscience · 2026Article
- From Deficiency to Therapy: Systemic Consequences of ALAS1 Disruption and the Protective Role of 5-ALA.Life (Basel, Switzerland) · 2025Review
- Article
- Modelling Peroxisomal Disorders in Zebrafish.Cells · 2025Review
- Peroxisomal import stress activates integrated stress response and inhibits ribosome biogenesis.PNAS nexus · 2024Article
- CYP51-mediated cholesterol biosynthesis is required for the proliferation of CD4Clinical and experimental medicine · 2023Article
- Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans.npj aging · 2023Article
- Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging.Antioxidants (Basel, Switzerland) · 2022Review
- Ether Lipids in Obesity: From Cells to Population Studies.Frontiers in physiology · 2022Review
- Murine deficiency of peroxisomal L-bifunctional protein (EHHADH) causes medium-chain 3-hydroxydicarboxylic aciduria and perturbs hepatic cholesterol homeostasis.Cellular and molecular life sciences : CMLS · 2021Article
- Beyond the cell factory: Homeostatic regulation of and by the UPRScience advances · 2020Review
- Metabolic interactions between peroxisomes and mitochondria with a special focus on acylcarnitine metabolism.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Peroxisome-Deficiency and HIF-2α Signaling Are Negative Regulators of Ketohexokinase Expression.Frontiers in cell and developmental biology · 2020Article
- Functional Peroxisomes Are Essential for Efficient Cholesterol Sensing and Synthesis.Frontiers in cell and developmental biology · 2020Article
- The peroxisome: an update on mysteries 2.0.Histochemistry and cell biology · 2018Review
- Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages.Cell death & disease · 2018Review
- Tauroursodeoxycholic bile acid arrests axonal degeneration by inhibiting the unfolded protein response in X-linked adrenoleukodystrophy.Acta neuropathologica · 2017Article
- Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis.The Journal of biological chemistry · 2015Article
- Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities.Stem cell research & therapy · 2015Article
- Hypoxia signaling pathways: modulators of oxygen-related organelles.Frontiers in cell and developmental biology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulation of hepatic cholesterol biosynthesis, lipogenesis, and insulin signaling intersect at the transcriptional level by control of SREBP and Insig genes. We previously demonstrated that peroxisome-deficient PEX2-/- mice activate SREBP-2 pathways but are unable to maintain normal cholesterol homeostasis. In this study, we demonstrate that oral bile acid treatment normalized hepatic and plasma cholesterol levels and hepatic cholesterol synthesis in early postnatal PEX2 mutants, but SREBP-2 and its target gene expressions remained increased. SREBP-2 pathway induction was also observed in neonatal and longer surviving PEX2 mutants, where hepatic cholesterol levels were normal. Abnormal expression patterns for SREBP-1c and Insig-2a, and novel regulation of Insig-2b, further demonstrate that peroxisome deficiency widely affects the regulation of related metabolic pathways. We have provided the first demonstration that peroxisome deficiency activates hepatic endoplasmic reticulum (ER) stress pathways, especially the integrated stress response mediated by PERK and ATF4 signaling. Our studies suggest a mechanism whereby ER stress leads to dysregulation of the endogenous sterol response mechanism and concordantly activates oxidative stress pathways. Several metabolic derangements in peroxisome-deficient PEX2-/- liver are likely to trigger ER stress, including perturbed flux of mevalonate metabolites, altered bile acid homeostasis, changes in fatty acid levels and composition, and oxidative stress.
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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.