Xlvii. the Role of Phospholipids in Electron Transfer*

A role for lipid in mitochondrial function has long been suspected and inferred (l-8). Coenzyme Q was the first lipid for which a requirement in electron transfer was clearly established (9). The requirement for coenzyme Q in respiration is readily demonstrable. It can be quantitatively extracted from mitochondria with acetone; concomitantly, respiration is abolished. Activity can be fully restored specifically by added coenzyme Q (10). However, coenzyme Q accounts for only 1% of the total lipids of mitochondria. In this paper, we shall concern ourselves with the essential role of the phospholipids that comprise more than 90% of the total lipids of beef heart mitochondria (11). Activating effects of various lipids, fatty acids, alcohols, aldehydes, and of detergents on preparations containing appreciable quantities of lipid have been frequently noted (e.g. 1%16a). Most, if not all, of these effects are irrelevant to the problem of lipid involvement in electron transfer. We decided that a sine qua non for proof of phospholipid involvement was (a) to remove the phospholipid; (b) to show a correlation between the removal and the loss of enzyme activity (electron transfer) ; (c) to show a correlation between restoration of activity and rebinding of phospholipid. Two developments made the completion of this undertaking possible. The first has to do with a suitable method for extraction of phospholipids from mitochondria (17). More than 80% of the phospholipid content can be extracted from mitochondria by aqueous acetone. Such mitochondria, designated as aqueous acetone-treated mitochondria, retain a small amount of their phospholipid and likewise show a small residual respiration. Respiration (succinic oxidase and succinate-cytochrome c reductase activity) could be restored by the addition of a “Q-lipoprotein” preparation (18) derived from beef heart mitochondria. The second development? was the recognition that the “Q-lipoprotein” is not a lipoprotein, 2 but is predominantly solubilized