ArticleMolecular metabolism2014
ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload.
Article in Molecular metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 152 citations in OpenAlex.
- Pomegranate seed oil attenuates palmitic acid-induced hepatic injury through modulation of oxidative stress: insights from GC-Q-TOF-MS-based metabolomics.Journal of the science of food and agriculture · 2026Article
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- Augmenter of Liver Regeneration-Modified Adipose Mesenchymal Stem Cell-Derived Exosomes Repairs Liver Damage by Regulating Endoplasmic Reticulum Stress and Pyroptosis in aAntioxidants (Basel, Switzerland) · 2026Article
- Hepatocyte TIA1 constrains metabolic steatohepatitis by translationally suppressing Srebf1 mRNA in stress granules.Cell death & disease · 2026Article
- Differential Effects of Saturated and Unsaturated Fatty Acids on Colorectal Cancer via IDO1 Signaling.Cancer medicine · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- Oxidative Stress in DNA Damage and Neurodegenerative Diseases: Unveiling The Mechanisms and Therapeutic Opportunities.Cell biochemistry and biophysics · 2025Review
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- SNRK modulates mTOR-autophagy pathway for liver lipid homeostasis in MAFLD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting BRD4 mitigates hepatocellular lipotoxicity by suppressing the NLRP3 inflammasome activation and GSDMD-mediated hepatocyte pyroptosis.Cellular and molecular life sciences : CMLS · 2024Article
- MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.bioRxiv : the preprint server for biology · 2024Article
- Spatiotemporally Precise Optical Manipulation of Intracellular Molecular Activities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Adipose-Derived Mesenchymal Stem Cells Protect Endothelial Cells from Hypoxic Injury by Suppressing Terminal UPR In Vivo and In Vitro.International journal of molecular sciences · 2023Article
- Abrupt Photoperiod Changes Differentially Modulate Hepatic Antioxidant Response in Healthy and Obese Rats: Effects of Grape Seed Proanthocyanidin Extract (GSPE).International journal of molecular sciences · 2023Article
- Linking the unfolded protein response to bioactive lipid metabolism and signalling in the cell non-autonomous extracellular communication of ER stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Phosphoinositides and intracellular calcium signaling: novel insights into phosphoinositides and calcium coupling as negative regulators of cellular signaling.Experimental & molecular medicine · 2023Review
- Unravelling the role of obesity and lipids during tumor progression.Frontiers in pharmacology · 2023Review
- Glial cell derived neurotrophic factor prevents western diet and palmitate-induced hepatocyte oxidative damage and death through SIRT3.Scientific reports · 2022Article
- Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress.Molecular biology reports · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Palmitate overload induces hepatic cell dysfunction characterized by enhanced apoptosis and altered citric acid cycle (CAC) metabolism; however, the mechanism of how this occurs is incompletely understood. We hypothesize that elevated doses of palmitate disrupt intracellular calcium homeostasis resulting in a net flux of calcium from the ER to mitochondria, activating aberrant oxidative metabolism. We treated primary hepatocytes and H4IIEC3 cells with palmitate and calcium chelators to identify the roles of intracellular calcium flux in lipotoxicity. We then applied (13)C metabolic flux analysis (MFA) to determine the impact of calcium in promoting palmitate-stimulated mitochondrial alterations. Co-treatment with the calcium-specific chelator BAPTA resulted in a suppression of markers for apoptosis and oxygen consumption. Additionally, (13)C MFA revealed that BAPTA co-treated cells had reduced CAC fluxes compared to cells treated with palmitate alone. Our results demonstrate that palmitate-induced lipoapoptosis is dependent on calcium-stimulated mitochondrial activation, which induces oxidative stress.
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