ArticleJournal of cell science2022
Lysosomal TRPML1 regulates mitochondrial function in hepatocellular carcinoma cells.
Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- How to Perform a Tracer Displacement BRET Assay for the TRPML1 Ion Channel.Bio-protocol · 2026Article
- Regulation of Ferroptosis Sensitivity in Hepatocellular Carcinoma Cells by Lysosomal Ion Channels TPC2 and TRPML1.Antioxidants (Basel, Switzerland) · 2026Article
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?Bioactive materials · 2025Review
- TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.Nature communications · 2025Article
- Biosynthesized Calcium Peroxide Nanoparticles as a Multifunctional Platform for Liver Cancer Therapy.International journal of molecular sciences · 2025Article
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Zephycandidine A and Synthetic Analogues-Synthesis and Evaluation of Biological Activity.Molecules (Basel, Switzerland) · 2025Article
- Loss of two-pore channel 2 enhances CD8+ T cell cytotoxicity and directly impairs tumour growth via MAPK axis in HCC.Frontiers in immunology · 2025Article
- Key Mechanisms in Lysosome Stability, Degradation and Repair.Molecular and cellular biology · 2025Review
- TPC2: From Blond Hair to Melanoma?Cancers · 2024Review
- Endolysosomal TRPML1 channel regulates cancer cell migration by altering intracellular trafficking of E-cadherin and βThe Journal of biological chemistry · 2024Article
- Endolysosomal transient receptor potential mucolipins and two-pore channels: implications for cancer immunity.Frontiers in immunology · 2024Review
- The Lysosomal Calcium Channel TRPML1 Maintains Mitochondrial Fitness in NK Cells through Interorganelle Cross-Talk.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- TRPML1 as a potential therapeutic target for triple-negative breast cancer: a review.Frontiers in oncology · 2023Review
- Prognostic Lysosome-Related Biomarkers for Predicting Drug Candidates in Hepatocellular Carcinoma: An Insilco Analysis.Journal of hepatocellular carcinoma · 2023Article
- Impaired autophagic flux and dedifferentiation in podocytes lacking Asah1 gene: Role of lysosomal TRPML1 channel.Biochimica et biophysica acta. Molecular cell research · 2023Article
- New Players in Neuronal Iron Homeostasis: Insights from CRISPRi Studies.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Liver cancers, including hepatocellular carcinoma (HCC), are the second leading cause of cancer death worldwide, and novel therapeutic strategies are still highly needed. Recently, the endolysosomal cation channel TRPML1 (also known as MCOLN1) has gained focus in cancer research because it represents an interesting novel target. We utilized the recently developed isoform-selective TRPML1 activator ML1-SA1 and the CRISPR/Cas9 system to generate tools for overactivation and loss-of-function studies on TRPML1 in HCC. After verification of our tools, we investigated the role of TRPML1 in HCC by studying proliferation, apoptosis and proteomic alterations. Furthermore, we analyzed mitochondrial function in detail by performing confocal and transmission electron microscopy combined with SeahorseTM and Oroboros® functional analysis. We report that TRPML1 overactivation mediated by a novel, isoform-selective small-molecule activator induces apoptosis by impairing mitochondrial function in a Ca2+-dependent manner. Additionally, TRPML1 loss-of-function deregulates mitochondrial renewal, which leads to proliferation impairment. Thus, our study reveals a novel role for TRPML1 as regulator of mitochondrial function and its modulators as promising molecules for novel therapeutic options in HCC therapy.
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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.