Journal article
In vivo isotope tracing reveals a requirement for the electron transport chain in glucose and glutamine metabolism by tumors
P Pachnis, Z Wu, B Faubert, A Tasdogan, W Gu, S Shelton, A Solmonson, AD Rao, AK Kaushik, TJ Rogers, JM Ubellacker, CA LaVigne, C Yang, B Ko, V Ramesh, J Sudderth, LG Zacharias, MS Martin-Sandoval, D Do, TP Mathews Show all
Science Advances | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2022
Open access
Abstract
In mice and humans with cancer, intravenous 13C-glucose infusion results in 13C labeling of tumor tricarboxylic acid (TCA) cycle intermediates, indicating that pyruvate oxidation in the TCA cycle occurs in tumors. The TCA cycle is usually coupled to the electron transport chain (ETC) because NADH generated by the cycle is reoxidized to NAD+ by the ETC. However, 13C labeling does not directly report ETC activity, and other pathways can oxidize NADH, so the ETC's role in these labeling patterns is unverified. We examined the impact of the ETC complex I inhibitor IACS-010759 on tumor 13C labeling. IACS-010759 suppresses TCA cycle labeling from glucose or lactate and increases labeling from glut..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was funded by the HHMI Investigator Program (S.J.M. and R.J.D.); Cancer Prevention and Research Institute of Texas (CPRIT) grant RP180778 (S.J.M. and R.J.D.); CPRIT grant RP170114 (S.J.M.); National Cancer Institute grants R35CA22044901, P50CA19651602, and 2P50CA070907-21A1 (R.J.D.); NIH grant U01 CA228608 (S.J.M.); NIH grant K99/R00 CA237724 (B.F.); NSF Graduate Research Fellowship grant 2019281210 (S.S.); NIH grant F99/K00 CA212230 (T.J.R.); German Research Foundation (DFG) Emmy Noether Award 467788900 (A.T.); Ministry of Culture and Science of the State of North Rhine-Westphalia NRW-Nachwuchsgruppenprogramm) funding (A.T.); and the Eunice Kennedy Shriver National Institute of Child Health and Human Development F32 HD096786-01 (A.S.).