ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2022
Inositol depletion regulates phospholipid metabolism and activates stress signaling in HEK293T cells.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Inositol biosynthesis is inversely regulated by glycolytic activity.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Article
- The functionality of the cysteinyl leukotriene receptor 1 (CysLTR1) in the lung by metabolomics analysis of bronchoalveolar lavage fluid.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Regulated Cell Death in Fungi, the Role of Metacaspases and Assay Techniques.Methods and protocols · 2026Review
- Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study.International journal of molecular sciences · 2025Article
- The Functionality of the Cysteinyl Leukotriene Receptor 1 (CysLTR1) in the Lung by Metabolomics Analysis of Bronchoalveolar Lavage Fluid.Research square · 2025Article
- Biallelic Loss-of-Function Variant inInternational journal of molecular sciences · 2025Article
- Article
- Divergent Molecular Responses to Heavy Water inPlants (Basel, Switzerland) · 2024Article
- Activated Inositol Phosphate, Substrate for Synthesis of Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)-The Key for the Effectiveness of Inositol-Feeding.International journal of molecular sciences · 2024Article
- Mechanistic insights into inositol-mediated rumen function promotion and metabolic alteration usingFrontiers in veterinary science · 2024Article
- The impacts of nicotinamide and inositol on the available cells and product performance of industrial baker's yeasts.Bioresources and bioprocessing · 2023Article
- Myo-Inositol and D-Chiro-Inositol as Modulators of Ovary Steroidogenesis: A Narrative Review.Nutrients · 2023Review
- The Role of Inositols in the Hyperandrogenic Phenotypes of PCOS: A Re-Reading of Larner's Results.International journal of molecular sciences · 2023Review
- Sunitinib versus Pazopanib Dilemma in Renal Cell Carcinoma: New Insights into the In Vitro Metabolic Impact, Efficacy, and Safety.International journal of molecular sciences · 2022Article
- The paradoxical role of inositol in cancer: a consequence of the metabolic state of a tumor.Cancer metastasis reviews · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Inositol plays a significant role in cellular function and signaling. Studies in yeast have demonstrated an "inositol-less death" phenotype, suggesting that inositol is an essential metabolite. In yeast, inositol synthesis is highly regulated, and inositol levels have been shown to be a major metabolic regulator, with its abundance affecting the expression of hundreds of genes. Abnormalities in inositol metabolism have been associated with several human disorders. Despite its importance, very little is known about the regulation of inositol synthesis and the pathways regulated by inositol in human cells. The current study aimed to address this knowledge gap. Knockout of ISYNA1 (encoding myo-inositol-3-P synthase 1) in HEK293T cells generated a human cell line that is deficient in de novo inositol synthesis. ISYNA1-KO cells exhibited inositol-less death when deprived of inositol. Lipidomic analysis identified inositol deprivation as a global regulator of phospholipid levels in human cells, including downregulation of phosphatidylinositol (PI) and upregulation of the phosphatidylglycerol (PG)/cardiolipin (CL) branch of phospholipid metabolism. RNA-Seq analysis revealed that inositol deprivation induced substantial changes in the expression of genes involved in cell signaling, including extracellular signal-regulated kinase (ERK), and genes controlling amino acid transport and protein processing in the endoplasmic reticulum (ER). This study provides the first in-depth characterization of the effects of inositol deprivation on phospholipid metabolism and gene expression in human cells, establishing an essential role for inositol in maintaining cell viability and regulating cell signaling and metabolism.
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