OXIDATIVE PHOSPHORYLATION AND COMPARTMENTATION OF FATTY ACID METABOLISM IN BROWN FAT MITOCHONDRIA

Mitochondria freshly isolated from brown adipose tissue by a standard procedure consistently fail to display normal oxidative phosphorylation. Incubation of these particles with ATP and carnitine in the absence of exogenous substrate results in a rapid burst of respiration which eventually slows to a low resting rate. Oxidation of the endogenous substrate is absolutely dependent upon the presence of both ATP and carnitine and is completely inhibited by rotenone. In the absence of added CoASH, respiration is also inhibited by atractyloside, and this inhibition in completely released by addition of CoASH. After the ATP + carnitine‐induced respiration has slowed to a low resting rate, oxidative phosphorylation is observed during the oxidation of added α‐ketoglutarate, succinate, or α‐glycerophosphate. If the mitochondria are incubated with ATP and carnitine in the presence of rotenone, coupled behavior is also observed upon subsequent oxidation of succinate or α‐glycerophosphate. Under appropriate conditions, the time‐course of appearance of oxidative phosphorylation corresponds closely to the time‐course of appearance of significant levels of acylcarnitine. It is concluded that the endogenous substrate of brown fat mitochondria is free fatty acids which lie initially outside the acyl‐CoA barrier, and that these are responsible for the uncoupled behavior of the freshly isolated particles. By providing the mitochondria with the appropriate components for activation and transport of free fatty acids, the redistribution which occurs relieves the uncoupling and hence both oxidative phosphorylation and classical sensitivities to inhibitors become evident. The significance of the fatty acid transport mechanism in these mitochondria is discussed with respect to a possible role in regulating the degree of uncoupling which may occur during active thermogenesis by brown adipose tissue. Copyright © 1969, Wiley Blackwell. All rights reserved