ArticleThe Journal of biological chemistry2013
Mitoferrin-2-dependent mitochondrial iron uptake sensitizes human head and neck squamous carcinoma cells to photodynamic therapy.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- SLC25A28 Ameliorates Hyperoxic Lung Injury by Improving Mitochondrial Oxidative Phosphorylation in Alveolar Epithelial Cells.International journal of molecular sciences · 2026Article
- Emerging links between TLR4 signaling and ferroptosis in heart failure.Frontiers in pharmacology · 2026Review
- Ferroptosis in cancer: revealing the multifaceted functions of mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- 2D and 3D in vitro photodynamic activities of tetra-substituted symmetric water-soluble cationic zinc(II) phthalocyanines on cancer.Scientific reports · 2025Article
- Mitochondrial Regulation of Ferroptosis in Cancer Cells.International journal of biological sciences · 2025Review
- STARD7 maintains intestinal epithelial mitochondria architecture, barrier integrity, and protection from colitis.JCI insight · 2024Article
- Role of ferroptosis in the pathogenesis of heart disease.Frontiers in physiology · 2024Review
- Oxidative stress induces mitochondrial iron overload and ferroptotic cell death.Scientific reports · 2023Article
- Membrane Transporters Involved in Iron Trafficking: Physiological and Pathological Aspects.Biomolecules · 2023Review
- Deficiency of mitochondrial calcium uniporter abrogates iron overload-induced cardiac dysfunction by reducing ferroptosis.Basic research in cardiology · 2023Article
- Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial Iron Metabolism: The Crucial Actors in Diseases.Molecules (Basel, Switzerland) · 2022Review
- Review
- FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation.Neurology. Genetics · 2022Article
- The Emerging Role of RNA N6-Methyladenosine Modification in Pancreatic Cancer.Frontiers in oncology · 2022Review
- Review
- Low Blue Dose Photodynamic Therapy with Porphyrin-Iron Oxide Nanoparticles Complexes: In Vitro Study on Human Melanoma Cells.Pharmaceutics · 2021Article
- Non-enzymatic lipid peroxidation initiated by photodynamic therapy drives a distinct ferroptosis-like cell death pathway.Redox biology · 2021Article
- Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Photodynamic therapy (PDT) is a promising approach to treat head and neck cancer cells. Here, we investigated whether mitochondrial iron uptake through mitoferrin-2 (Mfrn2) enhanced PDT-induced cell killing. Three human head and neck squamous carcinoma cell lines (UMSCC1, UMSCC14A, and UMSCC22A) were exposed to light and Pc 4, a mitochondria-targeted photosensitizer. The three cell lines responded differently: UMSCC1 and UMSCC14A cells were more resistant, whereas UMSCC22A cells were more sensitive to Pc 4-PDT-induced cell death. In non-erythroid cells, Mfrn2 is an iron transporter in the mitochondrial inner membrane. PDT-sensitive cells expressed higher Mfrn2 mRNA and protein levels compared with PDT-resistant cells. High Mfrn2-expressing cells showed higher rates of mitochondrial Fe(2+) uptake compared with low Mfrn2-expressing cells. Bafilomycin, an inhibitor of the vacuolar proton pump of lysosomes and endosomes that causes lysosomal iron release to the cytosol, enhanced PDT-induced cell killing of both resistant and sensitive cells. Iron chelators and the inhibitor of the mitochondrial Ca(2+) (and Fe(2+)) uniporter, Ru360, protected against PDT plus bafilomycin toxicity. Knockdown of Mfrn2 in UMSCC22A cells decreased the rate of mitochondrial Fe(2+) uptake and delayed PDT plus bafilomycin-induced mitochondrial depolarization and cell killing. Taken together, the data suggest that lysosomal iron release and Mfrn2-dependent mitochondrial iron uptake act synergistically to induce PDT-mediated and iron-dependent mitochondrial dysfunction and subsequent cell killing. Furthermore, Mfrn2 represents a possible biomarker of sensitivity of head and neck cancers to cell killing after PDT.
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