Identifying mitotane-induced mitochondria-associated membranes dysfunctions: metabolomic and lipidomic approaches.

ABSTRACT: Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner. Such alterations were very likely linked to the previously described, mitotane-induced respiratory chain defect. Lipidomic st

SUBMITTER: Hescot S 

PROVIDER: S-EPMC5746354 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature