Skip to main content
SpringerLink
Log in

Phytanic acid impairs mitochondrial respiration through protonophoric action

  • Research Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract.

Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    J. C. Komen & R. J. A. Wanders

  2. Departments of Membrane Biochemistry and Nijmegen Centres for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    F. Distelmaier, W. J. H. Koopman & P. H. M. G. Willems

  3. Departments of Pediatrics, Nijmegen Centres for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    F. Distelmaier & J. Smeitink

  4. Department of General Pediatrics, Heinrich-Heine-University, Düsseldorf, Germany

    F. Distelmaier

  5. Departments of Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    J. Smeitink

Authors
  1. J. C. Komen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Distelmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. H. Koopman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. J. A. Wanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Smeitink
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. H. M. G. Willems
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. C. Komen.

Additional information

Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007

J. C. Komen, F. Distelmaier: These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Komen, J.C., Distelmaier, F., Koopman, W.J.H. et al. Phytanic acid impairs mitochondrial respiration through protonophoric action. Cell. Mol. Life Sci. 64, 3271–3281 (2007). https://doi.org/10.1007/s00018-007-7357-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-007-7357-7

Keywords.

Search

Navigation