Bongkrekic Acid-a Review of a Lesser-Known Mitochondrial Toxin

Abstract

Introduction: Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning.

Methods: We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive.

Conclusions: Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.

Keywords: Bacterial toxin; Bongkrekic acid; Burkholderia cocovenenans; Food-borne illness; Mitochondrial toxin.

Fig. 1

Structure of bongkrekic acid

Fig. 2

Illustration of bongkrekic acid site of action showing inhibition of adenine nucleotide translocase in the mitochondrial matrix membrane