Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance.

ABSTRACT: Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemor

SUBMITTER: Giddings EL 

PROVIDER: S-EPMC8121950 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature