Induction of the mitochondrial permeability transition in vitro by short-chain carboxylic acids

C M Palmeira1, M I Rana, C B Frederick

  • 1Department of Biochemistry and Molecular Biology, University of Minnesota School of Medicine, Duluth 55812, USA.

Insights

Short-chain carboxylic acids, including acrylic acid, generally induce the mitochondrial permeability transition (MPT) in vitro. This effect is observed for acids with a pKa of 4 to 5 and is blocked by cyclosporine A.

Area of Science:

  • Biochemistry
  • Toxicology
  • Cell Biology

Background:

  • Acrylic acid (AA) was previously shown to induce mitochondrial permeability transition (MPT) in vitro.
  • This MPT induction was hypothesized to be crucial for acute inflammatory and hyperplastic responses in the olfactory epithelium.

Purpose of the Study:

  • To investigate whether MPT induction is a general response to short-chain carboxylic acids.
  • To identify critical physicochemical parameters governing MPT induction by these acids.

Main Methods:

  • Incubation of freshly isolated rat liver mitochondria with varying concentrations of selected carboxylic acids.
  • Assessment of MPT induction and its inhibition by cyclosporine A.

Main Results:

  • All tested carboxylic acids induced MPT in a concentration-dependent manner.
  • Cyclosporine A effectively blocked the MPT induction.
  • No significant correlation was found between MPT induction potency and saturation, octanol/water coefficient (log P), or dissociation constant (pKa), except for the general pKa range.

Conclusions:

  • MPT induction in vitro is a general response to short-chain carboxylic acids.
  • The critical factor for MPT induction appears to be the pKa of the carboxylic acid, specifically within the range of 4 to 5.

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