Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma.
acid sphingomyelinase
melanoma
mitochondrial dynamics
mitochondrial function
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
13
02
2020
revised:
20
03
2020
accepted:
28
03
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
26
2
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32244541
pii: cells9040848
doi: 10.3390/cells9040848
pmc: PMC7226741
pii:
doi:
Substances chimiques
acid sphingomyelinase-1
EC 3.1.4.-
Sphingomyelin Phosphodiesterase
EC 3.1.4.12
GTP Phosphohydrolases
EC 3.6.1.-
Mfn1 protein, mouse
EC 3.6.1.-
Opa1 protein, mouse
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing financial interests.
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