ArticleThe Biochemical journal2004
In brain mitochondria the branched-chain fatty acid phytanic acid impairs energy transduction and sensitizes for permeability transition.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 54 citations in OpenAlex.
- Metabolic Determinants of Cerebellar Circuit Formation and Maintenance.Cerebellum (London, England) · 2024Review
- Phytanic acid, an inconclusive phytol metabolite: A review.Current research in toxicology · 2023Article
- Phytol and its metabolites phytanic and pristanic acids for risk of cancer: current evidence and future directions.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2020Review
- Phytanic Acid-Induced Neurotoxicological Manifestations and Apoptosis Ameliorated by Mitochondria-Mediated Actions of Melatonin.Molecular neurobiology · 2017Article
- Brain Lipotoxicity of Phytanic Acid and Very Long-chain Fatty Acids. Harmful Cellular/Mitochondrial Activities in Refsum Disease and X-Linked Adrenoleukodystrophy.Aging and disease · 2016Review
- Peroxisomal Disorders: A Review on Cerebellar Pathologies.Brain pathology (Zurich, Switzerland) · 2015Review
- Disruption of mitochondrial homeostasis by phytanic acid in cerebellum of young rats.Cerebellum (London, England) · 2013Article
- Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease.Molecular and cellular biochemistry · 2012Article
- Relapsing encephalopathy in a patient with α-methylacyl-CoA racemase deficiency.BMJ case reports · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) accumulates at high levels throughout the body in the adult form of Refsum disease, a peroxisomal genetic disorder. However, it is still unclear why increased levels of phytanic acid have cytotoxic effects. In the present study, we examined the influence of non-esterified phytanic acid on energy-related functions of mitochondria from adult rat brain. Phytanic acid at low concentrations (5-20 microM, i.e. 5-20 nmol/mg of mitochondrial protein) de-energized mitochondria, as indicated by depolarization, stimulation of non-phosphorylating oxygen uptake and inhibition of the reduction of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. The unbranched homologue palmitic acid exerted much smaller effects. In addition, phytanic acid reduced state 3 respiration, which was partly due to inhibition of the ADP/ATP carrier. Phytanic acid decreased the rate of adenine nucleotide exchange and increased the degree of control, which the ADP/ATP carrier has on state 3 respiration. Important for functional consequences is the finding that mitochondria, which are preloaded with small amounts of Ca2+ (100 nmol/mg of protein), became highly sensitized to rapid permeability transition even when only low concentrations of phytanic acid (below 5 microM) were applied. In conclusion, the incorporation of phytanic acid into the inner mitochondrial membrane increases the membrane H+ conductance and disturbs the protein-linked functions in energy coupling. This is most probably essential for the short-term toxicity of phytanic acid. Thus in neural tissue, which becomes enriched with phytanic acid, the reduction in mitochondrial ATP supply and the facilitation of the opening of the permeability transition pore are two major mechanisms by which the branched-chain fatty acid phytanic acid induces the onset of degenerative processes.
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