The binding of dicyclohexylcarbodiimide to uncoupling protein in brown adipose tissue mitochondria

Abstract

The generation of heat in brown adipose tissue has been related to the uncoupling of respiration in their mitochondria (reviews [ 1,2]). The uncoupling in these mitochondria is achieved by a high ion conductance of the mitochondrial membrane and is specifically controlled by exogenous purine nucleotides [3-71. The binding site for these nucleotides was identified as a 32 000 Mr protein that is present in considerable amount only in brown adipose tissue mitochondria [S111. It is proposed that this protein (so called GDP-binding or uncoupling protein) is directly responsible for the physiological uncoupling of brown adipose tissue mitochondria. Here, we report that N,N’-dicyclohexylcarbodiimide a well-established inhibitor or proton-pumping activity of several membrane enzymes [12-161, binds rather specifically to the uncoupling protein in brown adipose tissue mitochondria. In addition, it inhibits the high chloride permeability of brown adipose tissue mitochondrial membrane. We propose that the 32 000 Mr uncoupling protein may function in mitochondrial membrane of brown adipose tissue similarly to other proton-translocating DCCD binding proteins.