Biochemical and cellular characterization of the CISD3 protein: Molecular bases of cluster release and destabilizing effects of nitric oxide

Grifagni, Deborah; Silva, José Malanho; Querci, Leonardo; Lepoivre, Michel; Vallières, Cindy; Louro, Ricardo O.; Banci, Lucia; Piccioli, Mario; Golinelli-Cohen, Marie-Pierre; Cantini, Francesca

doi:10.1016/j.jbc.2024.105745

Journal of Biological Chemistry

2024

DOI: 10.1016/j.jbc.2024.105745

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Biochemical and cellular characterization of the CISD3 protein: Molecular bases of cluster release and destabilizing effects of nitric oxide

Deborah Grifagni,

José Malanho Silva,

Leonardo Querci

et al.

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Cited by 3 publications

References 84 publications

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A novel (−)-(2S)-7,4′-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3

Munir,

Baig,

Razzaq

et al. 2024

Biogerontology

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A novel (−)-(2S)-7,4′-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3

Munir,

Baig,

Razzaq

et al. 2024

Biogerontology

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Structural aspects of iron‑sulfur protein biogenesis: An NMR view

Querci,

Piccioli,

Ciofi-Baffoni

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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CISD3 is a prognostic biomarker and therapeutic target in pan-cancer

Li,

Yang,

et al. 2024

Sci Rep

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Recent studies indicate that CISD3 is crucial in mitochondrial function and tumorigenesis. Using various databases, we systematically analyzed its expression, prognostic value, and immune activity. Our findings show CISD3 is mainly expressed in tumor cells across cancers, with higher mRNA but lower protein levels, degraded post-translationally via the lysosomal pathway. In certain cancers, CISD3 expression is positively correlated with tumor-infiltrating immune cells. Prognostic analysis suggests dual roles as both protective and risk factors, notably an independent prognostic predictor in renal cell carcinoma (RCC). CISD3 copy number variations are linked to homologous recombination defects and tumor-specific neoantigens, negatively correlated with methylation levels. Pathway analysis reveals CISD3 involvement in oncogenic processes, such as proliferation inhibition and epithelial-mesenchymal transition. Protein interactions underline its role in mitochondrial metabolism and redox balance. Experiments confirm low CISD3 expression in cancers, with overexpression reducing proliferation, migration, invasion, and tumor growth in mice. Mechanistic studies indicate CISD3 overexpression disrupts mitochondrial function, increases ROS levels, decreases GSH/GSSG ratios and mitochondrial membrane potential, inhibiting antioxidant activity and promoting cell damage and ferroptosis, thus impeding cancer progression. This study highlights CISD3’s potential as a prognostic biomarker and therapeutic target. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-74247-1.

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Biochemical and cellular characterization of the CISD3 protein: Molecular bases of cluster release and destabilizing effects of nitric oxide

Cited by 3 publications

References 84 publications

A novel (−)-(2S)-7,4′-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3

A novel (−)-(2S)-7,4′-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3

Structural aspects of iron‑sulfur protein biogenesis: An NMR view

CISD3 is a prognostic biomarker and therapeutic target in pan-cancer

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