Disruption of mitochondrial homeostasis by phytanic acid in cerebellum of young rats.

Abstract

Phytanic acid (Phyt) brain concentrations are highly increased in Refsum disease, a peroxisomal disorder clinically characterized by neurological features, cardiac abnormalities, and retinitis pigmentosa. Considering that the pathogenesis of cerebellar ataxia, a common finding in this disease, is still unknown, in the present work we investigated the in vitro effects of Phyt at concentrations similar to those found in affected patients on important parameters of mitochondrial homeostasis in cerebellum from young rats. The respiratory parameters states 3 and 4 and respiratory control ratio (RCR) determined by oxygen consumption, membrane potential (∆Ψm), NAD(P)H pool content, and swelling were evaluated in mitochondrial preparations from this cerebral structure. Phyt markedly increased state 4 respiration, whereas state 3 respiration, the RCR, the mitochondrial matrix NAD(P)H content, and ∆Ψm were decreased by this fatty acid, being the latter effect partially prevented by N-acetylcysteine. These data indicate that Phyt behaves as an uncoupler of oxidative phosphorylation and as a metabolic inhibitor disrupting mitochondrial homeostasis in cerebellum. It is proposed that these pathomechanisms may contribute at least in part to the cerebellar alterations found in Refsum disease.

• Authors: Estela Natacha Brandt Busanello, Alexandre Umpierrez Amaral, Anelise Miotti Tonin, Angela Zanatta, Carolina Maso Viegas, Carmen Regla Vargas, Moacir Wajner
• Journal: Cerebellum (London, England) (Cerebellum) Vol. 12 Issue 3 Pg. 362-9 (Jun 2013) ISSN: 1473-4230 [Electronic] United States
• PMID: 23081695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ketoglutaric Acids
• Phytanic Acid
• Glutamic Acid
• NADP
• Adenosine Diphosphate

Topics

• Adenosine Diphosphate (pharmacology)
• Animals
• Cerebellum (ultrastructure)
• Dose-Response Relationship, Drug
• Glutamic Acid (pharmacology)
• Homeostasis (drug effects)
• Ketoglutaric Acids (pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, pathology)
• NADP (metabolism)
• Oxygen Consumption (drug effects)
• Phytanic Acid (pharmacology)
• Rats
• Rats, Wistar
• Statistics, Nonparametric