Binding of bilirubin with lipid. A possible mechanism of its toxic reactions in mitochondria.

Binding of bilirubin with mitochondria, mitochondrial membranes, various cells, and cellular fragments resulted in a hypochromicity with a red shift of the absorption spectrum of bilirubin. It was found that the mitochondrial lipids rather than the proteins were involved in the binding. Isolated mitochondrial lipid and lipids from various other sources caused similar spectral changes of the bilirubin absorbance. Exogenous lipid could prevent the toxic effect of bilirubin on well defined mitochondrial reactions as did serum albumin. Washing of bilirubin-treated mitochondria with albumin restored their normal function to a considerable extent. Thest findings suggest that the binding of bilirubin with lipid alters the characteristics of mitochondrial membranes so that membrane-linked functions are impaired. In view of the lipophilic nature of bilirubin, this explanation might be considered as a mechanism of toxicity of bilirubin for cells in general.