Observation of acetyl phosphate formation in mammalian mitochondria using real-time in-organelle NMR metabolomics

Wen Jun Xu, He Wen, Han Sun Kim, Yoon Joo Ko, Seung Mo Dong, In Sun Park, Jong In Yook, Sunghyouk Park

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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 and13C3-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 acetyl-CoA 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.

Original languageEnglish
Pages (from-to)4152-4157
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number16
DOIs
Publication statusPublished - 2018 Apr 17

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. The research was supported by grants to S.P. from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (2014-069340 and 2009-83533); the National R&D Program for Cancer Control (1420290); and the Bio-Synergy Research Project (NRF-2015M3A9C4075818) of the Ministry of Science, Information and Communication Technology, and Future Planning through the National Research Foundation of Korea.

Funding Information:
The research was supported by grants to S.P. from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (2014-069340 and 2009-83533); the National R&D Program for Cancer Control (1420290); and the Bio-Synergy Research Project (NRF-2015M3A9C4075818) of the Ministry of Science, Information and Communication Technology, and Future Planning through the National Research Foundation of Korea.

Publisher Copyright:
© 2018 National Academy of Sciences. All Rights Reserved.

All Science Journal Classification (ASJC) codes

  • General

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