Doxorubicin Inhibits Phosphatidylserine Decarboxylase and Modifies Mitochondrial Membrane Composition in HeLa Cells.
bioenergetics
doxorubicin
phosphatidylethanolamine
phosphatidylserine decarboxylase
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Feb 2020
15 Feb 2020
Historique:
received:
06
01
2020
revised:
11
02
2020
accepted:
13
02
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
24
11
2020
Statut:
epublish
Résumé
Doxorubicin (DXR) is a drug widely used in chemotherapy. Its mode of action is based on its intercalation properties, involving the inhibition of topoisomerase II. However, few studies have reported the mitochondrial effects of DXR while investigating cardiac toxicity induced by the treatment, mostly in pediatric cases. Here, we demonstrate that DXR alters the mitochondrial membrane composition associated with bioenergetic impairment and cell death in human cancer cells. The remodeling of the mitochondrial membrane was explained by phosphatidylserine decarboxylase (PSD) inhibition by DXR. PSD catalyzes phosphatidylethanolamine (PE) synthesis from phosphatidylserine (PS), and DXR altered the PS/PE ratio in the mitochondrial membrane. Moreover, we observed that DXR localized to the mitochondrial compartment and drug uptake was rapid. Evaluation of other topoisomerase II inhibitors did not show any impact on the mitochondrial membrane composition, indicating that the DXR effect was specific. Therefore, our findings revealed a side molecular target for DXR and PSD, potentially involved in DXR anti-cancer properties and the associated toxicity.
Identifiants
pubmed: 32075281
pii: ijms21041317
doi: 10.3390/ijms21041317
pmc: PMC7072979
pii:
doi:
Substances chimiques
Phosphatidylethanolamines
0
Phosphatidylserines
0
phosphatidylethanolamine
39382-08-6
Doxorubicin
80168379AG
Carboxy-Lyases
EC 4.1.1.-
phosphatidylserine decarboxylase
EC 4.1.1.65
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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