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Article

Acute Increases in Intracellular Zinc Lead to an Increased Lysosomal and Mitochondrial Autophagy and Subsequent Cell Demise in Malignant Melanoma

Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Zborovska 2089, 500 03 Hradec Kralove, Czech Republic
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 667; https://doi.org/10.3390/ijms22020667
Received: 27 November 2020 / Revised: 28 December 2020 / Accepted: 6 January 2021 / Published: 11 January 2021
(This article belongs to the Special Issue Autophagy in Health, Ageing and Disease 2.0)
Changes in zinc content and dysregulated zinc homeostatic mechanisms have been recognized in several solid malignancies such as prostate cancer, breast cancer, or pancreatic cancer. Moreover, it has been shown that zinc serum and/or tissue levels are altered in melanoma with varying effects on melanoma development and biology. This study was conducted to explore the effects of acute increases of intracellular zinc in a set of melanoma tissue explants obtained from clinical samples. Measurements of their zinc content showed an extant heterogeneity in total and free intracellular zinc pools associated with varying biological behavior of individual cells, e.g., autophagy levels and propensity to cell death. Use of zinc pyrithione elevated intracellular zinc in a short time frame which resulted in marked changes in mitochondrial activity and lysosomes. These alterations were accompanied by significantly enhanced autophagy flux and subsequent cell demise in the absence of typical apoptotic cell death markers. The present results show for the first time that acutely increased intracellular zinc in melanoma cells specifically enhances their autophagic activity via mitochondria and lysosomes which leads to autophagic cell death. While biologically relevant, this discovery may contribute to our understanding and exploration of zinc in relation to autophagy as a means of controlling melanoma growth and survival. View Full-Text
Keywords: zinc; melanoma; autophagy; cell death; mitochondria; lysosomes zinc; melanoma; autophagy; cell death; mitochondria; lysosomes
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MDPI and ACS Style

Rudolf, E.; Rudolf, K. Acute Increases in Intracellular Zinc Lead to an Increased Lysosomal and Mitochondrial Autophagy and Subsequent Cell Demise in Malignant Melanoma. Int. J. Mol. Sci. 2021, 22, 667. https://doi.org/10.3390/ijms22020667

AMA Style

Rudolf E, Rudolf K. Acute Increases in Intracellular Zinc Lead to an Increased Lysosomal and Mitochondrial Autophagy and Subsequent Cell Demise in Malignant Melanoma. International Journal of Molecular Sciences. 2021; 22(2):667. https://doi.org/10.3390/ijms22020667

Chicago/Turabian Style

Rudolf, Emil, and Kamil Rudolf. 2021. "Acute Increases in Intracellular Zinc Lead to an Increased Lysosomal and Mitochondrial Autophagy and Subsequent Cell Demise in Malignant Melanoma" International Journal of Molecular Sciences 22, no. 2: 667. https://doi.org/10.3390/ijms22020667

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