ArticleCell communication and signaling : CCS2019
Connecting lysosomes and mitochondria - a novel role for lipid metabolism in cancer cell death.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- The lipidomic atlas for cellular organelles to reveal the central role of mitochondria in organelle communication.Science China. Life sciences · 2026Article
- Regulation of Ferroptosis Sensitivity in Hepatocellular Carcinoma Cells by Lysosomal Ion Channels TPC2 and TRPML1.Antioxidants (Basel, Switzerland) · 2026Article
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- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
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- Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance.Journal of the National Cancer Center · 2025Review
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Real-Time Monitoring of Adenosine Triphosphate Fluctuation in Lysosome during Autophagy/Mitophagy.ACS applied materials & interfaces · 2025Article
- Chondroitin Sulfate as a Lysosomal Enhancer Attenuates Lipid-Driven Inflammation via Lipophagy and Mitophagy.Marine drugs · 2025Article
- Lysosomal-Mitochondrial Interaction Promotes Tumor Growth in Squamous Cell Carcinoma of the Head and Neck.Molecular cancer research : MCR · 2025Article
- Role of lipids in interorganelle communication.Trends in cell biology · 2025Review
- 4-Aminoquinoline: a comprehensive review of synthetic strategies.Frontiers in chemistry · 2025Review
- Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Role of Mitochondrial Reactive Oxygen Species-Mediated Chaperone-Mediated Autophagy and Lipophagy in Baicalin and N-Acetylcysteine Mitigation of Cadmium-Induced Lipid Accumulation in Liver.Antioxidants (Basel, Switzerland) · 2024Article
- Effect of mitochondrial circulation on mitochondrial age density distribution.International journal for numerical methods in biomedical engineering · 2023Article
- Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells.International journal of molecular sciences · 2023Article
- Clofazimine-Mediated, Age-Related Changes in Skeletal Muscle Mitochondrial Metabolites.Metabolites · 2023Article
- The helminth derived peptide FhHDM-1 redirects macrophage metabolism towards glutaminolysis to regulate the pro-inflammatory response.Frontiers in immunology · 2023Article
- A metabolic shift toward glycolysis enables cancer cells to maintain survival upon concomitant glutamine deprivation and V-ATPase inhibition.Frontiers in nutrition · 2023Article
- AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1.Nature communications · 2022Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.
methodsLC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements.
resultsOur data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells.
conclusionThis study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors.
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