Summary of project PR001108

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001108. The data can be accessed directly via it's Project DOI: 10.21228/M8GM5B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001108
Project DOI:doi: 10.21228/M8GM5B
Project Title:Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance
Project Summary:Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing 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 MCJ (DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed novel MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an new strategy for treatment of multiple cancers.
Institute:University of Colorado Denver
Department:Biochemistry and Molecular Genetics
Laboratory:Angelo D'Alessandro
Last Name:Culp-Hill
First Name:Rachel
Address:12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
Email:rachel.hill@cuanschutz.edu
Phone:303-724-5798

Summary of all studies in project PR001108

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST001730 Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance Homo sapiens University of Colorado Denver MS 2021-03-31 1 8 Uploaded data (639.7M)*
ST001731 Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance (part-II) Homo sapiens University of Colorado Denver MS 2021-03-31 1 8 Uploaded data (528.5M)*
ST001732 Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance (part-III) Homo sapiens University of Colorado Anschutz Medical Campus MS 2021-03-31 1 8 Uploaded data (260.6M)*
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