Summary of Study ST001730

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.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001730
Study TitleMitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance
Study SummaryChemotherapy 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
DepartmentBiochemistry and Molecular Genetics
LaboratoryAngelo D'Alessandro
Last NameCulp-Hill
First NameRachel
Address12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
Emailrachel.hill@cuanschutz.edu
Phone303-724-5798
Submit Date2021-03-17
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-03-31
Release Version1
Rachel Culp-Hill Rachel Culp-Hill
https://dx.doi.org/10.21228/M8GM5B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN002815 AN002816
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Relative Abundance Relative Abundance

MS:

MS ID:MS002609
Analysis ID:AN002815
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:UHPLC was coupled in line with a high-resolution quadrupole Orbitrap instrument run in positive polarity mode (QExactive, Thermo Fisher) at 70,000 resolution (at 200 m/z). Gradients and other technical parameters and the variants employed herein have been extensively described.
Ion Mode:POSITIVE
  
MS ID:MS002610
Analysis ID:AN002816
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:UHPLC was coupled in line with a high-resolution quadrupole Orbitrap instrument run in negative polarity mode (QExactive, Thermo Fisher) at 70,000 resolution (at 200 m/z). Gradients and other technical parameters and the variants employed herein have been extensively described.
Ion Mode:NEGATIVE
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