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Article

Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma

by
Marco Coazzoli
1,†,
Alessandra Napoli
1,2,†,
Paulina Roux-Biejat
1,†,
Clara De Palma
3,
Claudia Moscheni
1,
Elisabetta Catalani
4,
Silvia Zecchini
1,
Vincenzo Conte
5,
Matteo Giovarelli
1,
Sonia Caccia
1,
Patrizia Procacci
5,
Davide Cervia
4,
Emilio Clementi
1,6,* and
Cristiana Perrotta
1,*
1
Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università degli Studi di Milano, 20157 Milano, Italy
2
Unit of Clinical Pharmacology, University Hospital “Luigi Sacco”-ASST Fatebenefratelli Sacco, 20157 Milano, Italy
3
Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milano, Italy
4
Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, Italy
5
Department of Biomedical Sciences for Health (SCIBIS), Università degli Studi di Milano, 20133 Milano, Italy
6
Scientific Institute IRCCS “Eugenio Medea”, 23842 Bosisio Parini, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2020, 9(4), 848; https://doi.org/10.3390/cells9040848
Submission received: 13 February 2020 / Revised: 20 March 2020 / Accepted: 28 March 2020 / Published: 31 March 2020
(This article belongs to the Special Issue Sphingolipids in Cancer Progression and Therapy)
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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.
Keywords: melanoma; acid sphingomyelinase; mitochondrial dynamics; mitochondrial function melanoma; acid sphingomyelinase; mitochondrial dynamics; mitochondrial function

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MDPI and ACS Style

Coazzoli, M.; Napoli, A.; Roux-Biejat, P.; De Palma, C.; Moscheni, C.; Catalani, E.; Zecchini, S.; Conte, V.; Giovarelli, M.; Caccia, S.; et al. Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma. Cells 2020, 9, 848. https://doi.org/10.3390/cells9040848

AMA Style

Coazzoli M, Napoli A, Roux-Biejat P, De Palma C, Moscheni C, Catalani E, Zecchini S, Conte V, Giovarelli M, Caccia S, et al. Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma. Cells. 2020; 9(4):848. https://doi.org/10.3390/cells9040848

Chicago/Turabian Style

Coazzoli, Marco, Alessandra Napoli, Paulina Roux-Biejat, Clara De Palma, Claudia Moscheni, Elisabetta Catalani, Silvia Zecchini, Vincenzo Conte, Matteo Giovarelli, Sonia Caccia, and et al. 2020. "Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma" Cells 9, no. 4: 848. https://doi.org/10.3390/cells9040848

APA Style

Coazzoli, M., Napoli, A., Roux-Biejat, P., De Palma, C., Moscheni, C., Catalani, E., Zecchini, S., Conte, V., Giovarelli, M., Caccia, S., Procacci, P., Cervia, D., Clementi, E., & Perrotta, C. (2020). Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma. Cells, 9(4), 848. https://doi.org/10.3390/cells9040848

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