Email updates

Keep up to date with the latest news and content from BMC Research Notes and BioMed Central.

Open Access Open Badges Short Report

Effect of bilirubin on cytochrome c oxidase activity of mitochondria from mouse brain and liver

Safarina G Malik1*, K Astrid Irwanto1, J Donald Ostrow2 and Claudio Tiribelli3

Author Affiliations

1 Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia

2 GI/Hepatology Division, Dept. Medicine, University of Washington, Seattle, WA, 98195, USA

3 CSF AREA Science Park and Dept. ACADEM, University of Trieste, 34012, Trieste, Italy

For all author emails, please log on.

BMC Research Notes 2010, 3:162  doi:10.1186/1756-0500-3-162

Published: 9 June 2010



The unbound, free concentration (Bf) of unconjugated bilirubin (UCB), and not the total UCB level, has been shown to correlate with bilirubin cytotoxicity, but the key molecular mechanisms accounting for the toxic effects of UCB are largely unknown.


Mouse liver mitochondria increase unbound UCB oxidation, consequently increasing the apparent rate constant for unbound UCB oxidation by HRP (Kp), higher than in control and mouse brain mitochondria, emphasizing the importance of determining Kp in complete systems containing the organelles being studied. The in vitro effects of UCB on cytochrome c oxidase activity in mitochondria isolated from mouse brain and liver were studied at Bf ranging from 22 to 150 nM. The results show that UCB at Bf up to 60 nM did not alter mitochondrial cytochrome c oxidase activity, while the higher concentrations significantly inhibited the enzyme activity by 20% in both liver and brain mitochondria.


We conclude that it is essential to include the organelles being studied in the medium used in measuring both Kp and Bf. A moderately elevated, pathophysiologically-relevant Bf impaired the cytochrome c oxidase activity modestly in mitochondria from mouse brain and liver.