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Detection of liver mitochondrial oxaloacetate by NMR spectroscopy and membrane potential‐dependent accumulation
Journal article   Open access   Peer reviewed

Detection of liver mitochondrial oxaloacetate by NMR spectroscopy and membrane potential‐dependent accumulation

Liping Yu, Brian D. Fink and William I. Sivitz
The FASEB journal, Vol.39(7), e70490
04/15/2025
DOI: 10.1096/fj.202500039R
PMCID: PMC11959514
PMID: 40166919
Appears in  UI Libraries Support Open Access
url
https://doi.org/10.1096/fj.202500039RView
Published (Version of record) Open Access

Abstract

Oxaloacetate (OAA) is a central liver metabolite fundamental to critical metabolic pathways. However, understanding OAA metabolism in the liver has been limited because the compound is very difficult to measure by mass spectroscopy and not abundant enough for detection by other methods. Here we describe a novel approach to quantifying OAA in liver mitochondria. Moreover, we provide evidence for membrane potential‐dependent OAA accumulation in mitochondria during complex II—energized respiration consistent with OAA inhibition of succinate dehydrogenase. Oxaloacetate is centrally positioned in the TCA cycle to regulate critical steps towards whole‐body physiology. Nonetheless, studies of OAA metabolism in the liver are severely limited because OAA is unstable and very difficult to measure by mass spectrometry and too low to detect by conventional procedures.
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