Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 16, Pages 4152-4157Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1720908115
Keywords
real time; metabolomics; NMR; mitochondria; acetyl phosphate
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Funding
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science, and Technology [2014-069340, 2009-83533]
- National R&D Program for Cancer Control of the Ministry of Science, Information and Communication Technology, and Future Planning through the National Research Foundation of Korea [1420290]
- Bio-Synergy Research Project of the Ministry of Science, Information and Communication Technology, and Future Planning through the National Research Foundation of Korea [NRF-2015M3A9C4075818]
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Recent studies point out the link between altered mitochondrial metabolism and cancer, and detailed understanding of mitochondrial metabolism requires real-time detection of its metabolites. Employing heteronuclear 2D NMR spectroscopy and C-13(3)-pyruvate, we propose in-organelle metabolomics that allows for the monitoring of mitochondrial metabolic changes in real time. The approach identified acetyl phosphate from human mitochondria, whose production has been largely neglected in eukaryotic metabolism since its first description about 70 years ago in bacteria. The kinetic profile of acetyl phosphate formation was biphasic, and its transient nature suggested its role as a metabolic intermediate. The method also allowed for the estimation of pyruvate dehydrogenase (PDH) enzyme activity through monitoring of the acetylCoA formation, independent of competing cytosolic metabolism. The results confirmed the positive regulation of mitochondrial PDH activity by p53, a well-known tumor suppressor. Our approach can easily be applied to other organelle-specific metabolic studies.
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