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Updated: Jul 28, 2025

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues
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Novel dicarbonyl metabolic pathway via mitochondrial ES1 possessing glyoxalase III activity

Ginga Ito1, Yota Tatara2, Ken Itoh2

  • 1Department of Biological Science, Graduate School of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan.

BBA Advances
|May 30, 2023
PubMed

Insights

Mitochondrial protein ES1 demonstrates glyoxalase III (GLO3) activity, crucial for metabolizing reactive dicarbonyls like glyoxal. This discovery reveals a new pathway for dicarbonyl metabolism within mitochondria.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Mitochondrial Metabolism

Background:

  • Reactive dicarbonyls, such as glyoxal (GO) and methylglyoxal (MGO), are metabolic byproducts implicated in disease via advanced glycation end product formation.
  • The metabolic pathways for these dicarbonyls within mitochondria are not well understood.
  • Mammalian mitochondrial protein ES1 is hypothesized to be a homolog of bacterial elbB, possessing glyoxalase III (GLO3) activity.

Purpose of the Study:

  • To investigate the function of mammalian mitochondrial protein ES1.
  • To determine if ES1 possesses glyoxalase III (GLO3) activity.
  • To elucidate the role of ES1 in mitochondrial dicarbonyl metabolism.

Main Methods:

  • Generation of ES1-knockout (KO) mice and recombinant mouse ES1 protein.
  • Biochemical analyses of mitochondrial fractions from wildtype (WT) and ES1-KO mouse brains.
  • Histological and proteomic analyses of mitochondrial fractions.
  • Assay of recombinant ES1 protein for catalytic activity.

Main Results:

  • Mitochondrial fractions from ES1-KO mouse brains showed significantly lower glyoxal (GO) metabolism and cytochrome c oxidase activity compared to WT.
  • Mitochondrial morphology remained largely unchanged in ES1-KO mouse brains.
  • Mitochondrial proteome analysis revealed increased MGO degradation III pathway and oxidative phosphorylation proteins in ES1-KO mice.
  • Recombinant mouse ES1 protein demonstrated catalytic activity in converting GO to glycolic acid.

Conclusions:

  • ES1 possesses glyoxalase III (GLO3) activity, playing a key role in metabolizing glyoxal (GO) within mitochondria.
  • ES1 modulates mitochondrial dicarbonyl metabolism and is linked to cytochrome c oxidase activity.
  • This study identifies a novel mitochondrial pathway for reactive dicarbonyl metabolism.
Keywords:
ES1GlyoxalaseMethylglyoxal degradationMitochondriaReactive dicarbonyl

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