Inhibition of the mitochondrial permeability transition by aldehydes

William A. Irwin, Lawrence D. Gaspers, John A. Thomas, William A. Irwin, Lawrence D. Gaspers

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Fructose has been shown to protect hepatocyte viability during hypoxia or exposure to mitochondrial electron transport inhibitors. We report here that the fructose metabolite D-glyceraldehyde (D-GA) is a good inhibitor of the mitochondrial permeability transition pore (PTP) in isolated rat liver mitochondria. We propose that a substantial portion of the protective effect of fructose on hepatocytes is due to D-GA inhibition of the permeability transition. Aldehydes which are substrates of the mitochondrial aldehyde dehydrogenase (mALDH) afford protection, while poor substrates do not. Protection is prevented by the ALDH inhibitor chloral hydrate. We propose that the NADH/NAD+ ratio is the key to protection. The aldehydes phenylglyoxal (PGO) and 4-hydroxynonenal (4-HNE), which have previously been shown to inhibit the PTP, apparently function by a different mechanism independent of mALDH activity. Both PGO or 4-HNE are themselves potent inhibitors of ALDH, and their protective effect cannot be blocked by an ALDH inhibitor.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume291
Issue number2
DOIs
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Aldehyde
  • Aldehydes
  • Dehydrogenase
  • Fructose
  • Hepatocytes
  • Mitochondrial permeability transition

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