BMCP1: a mitochondrial uncoupling protein in neurons which regulates mitochondrial function and oxidant production

Outside the nervous system, members of the mitochondrial uncoupling protein (UCP) family have been proposed to contribute to control of body temperatu re and energy metabolism, and regulation of mitochondrial production of rea ctive oxygen species (ROS). However, the function of brain mitochondrial ca rrier protein 1 (BMCP1), which is highly expressed in brain, remains to be determined. To study BMCP1 expression and function in the nervous system, a high-affinity antibody to BMCP1 was generated and used to analyze tissue e xpression of BMCP1 protein in mouse. BMCP1 protein was highly expressed in heart and kidney, but not liver or lung. In the nervous system, BMCP1 was p resent in cortex, basal ganglia, substantia nigra, cerebellum, and spinal c ord. Both BMCP1 mRNA and protein xpression was almost exclusively neuronal. To study the effect of BMCP1 expression on mitochondrial function, neurona l (GT1-1) cell lines with stable overexpression of BMCP1 were generated. Tr ansfected cells had higher State 4 respiration and lower mitochondrial memb rane potential (psi (m)), consistent with greater mitochondrial uncoupling. BMCP1 expression also decreased mitochondrial production of ROS. These dat a suggest that BMCP1 can modify mitochondrial respiratory efficiency and mi tochondrial oxidant production, and raise the possibility that BMCP1 might alter the vulnerability of brain to both acute injury and to neurodegenerat ive conditions.