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

Authors
 Wen Jun Xu  ;  He Wen  ;  Han Sun Kim  ;  Yoon-Joo Ko  ;  Seung-Mo Dong  ;  In-Sun Park  ;  Jong In Yook  ;  Sunghyouk Park 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.115(16) : 4152-4157, 2018 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2018
Keywords
NMR ; acetyl phosphate ; metabolomics ; mitochondria ; real time
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 and 13C3-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.
Files in This Item:
T201805435.pdf Download
DOI
10.1073/pnas.1720908115
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167268
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