Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/43494
Title: Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma
Authors: Coazzoli, Marco
Napoli, Alessandra
Roux-Biejat, Paulina
Palma, Clara De
Moscheni, Claudia
Catalani, Elisabetta
Zecchini, Silvia
Conte, Vincenzo
Giovarelli, Matteo
Caccia, Sonia
Procacci, Patrizia
Cervia, Davide 
Clementi, Emilio
Perrotta, Cristiana
Journal: CELLS 
Issue Date: 2020
Abstract: 
Melanoma is the most severe type of skin cancer. Its unique and heterogeneous metabolism, relying on both glycolysis and oxidative phosphorylation, allows it to adapt to disparate conditions. Mitochondrial function is strictly interconnected with mitochondrial dynamics and both are fundamental in tumour progression and metastasis. The malignant phenotype of melanoma is also regulated by the expression levels of the enzyme acid sphingomyelinase (A-SMase). By modulating at transcriptional level A-SMase in the melanoma cell line B16-F1 cells, we assessed the effect of enzyme downregulation on mitochondrial dynamics and function. Our results demonstrate that A-SMase influences mitochondrial morphology by affecting the expression of mitofusin 1 and OPA1. The enhanced expression of the two mitochondrial fusion proteins, observed when A-SMase is expressed at low levels, correlates with the increase of mitochondrial function via the stimulation of the genes PGC-1alpha and TFAM, two genes that preside over mitochondrial biogenesis. Thus, the reduction of A-SMase expression, observed in malignant melanomas, may determine their metastatic behaviour through the stimulation of mitochondrial fusion, activity and biogenesis, conferring a metabolic advantage to melanoma cells.
URI: http://hdl.handle.net/2067/43494
ISSN: 2073-4409
DOI: 10.3390/cells9040848
Rights: Attribution-NonCommercial-NoDerivs 3.0 United States
Appears in Collections:A1. Articolo in rivista

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