UCP4 is a member of the mitochondrial uncoupling protein subfamily and one of the three UCPs (UCP2, UCP4, UCP5), associated with the nervous system. Its putative functions include thermogenesis, attenuation of reactive oxidative species (ROS), regulation of mitochondrial calcium concentration and involvement in cell differentiation and apoptosis. Here we investigate UCP4"s subcellular, cellular and tissue distribution, using an antibody designed specially for this study, and discuss the findings in terms of the protein"s possible functions. Western blot and immunohistochemistry data confirmed that UCP4 is expressed predominantly in the central nervous system (CNS), as previously shown at mRNA level. No protein was found in heart, spleen, stomach, intestine, lung, thymus, muscles, adrenal gland, testis and liver. The reports revealing UCP4 mRNA in kidney and white adipose tissue were not confirmed at protein level. The amount of UCP4 varies in the mitochondria of different brain regions, with the highest protein content found in cortex. We show that UCP4 is present in fetal murine brain tissue as early as embryonic days 12-14 (E12-E14), which coincides with the beginning of neuronal differentiation. The UCP4 content in mitochondria decreases as the age of mice increases. UCP4 preferential expression in neurons and its developmental expression pattern under physiological conditions may indicate a specific protein function, e.g. in neuronal cell differentiation.
Age Factors Amino Acid Sequence Animals Blotting, Western Cell Differentiation Embryo, Mammalian/cytology Embryo, Mammalian/metabolism* Female Gene Expression Regulation, Developmental Immunoenzyme Techniques Immunoglobulin G/immunology Ion Channels/genetics Ion Channels/immunology Ion Channels/metabolism* Mice Mice, Inbred C57BL Mitochondria/metabolism* Mitochondrial Proteins/genetics Mitochondrial Proteins/immunology Mitochondrial Proteins/metabolism* Molecular Sequence Data Neurons/cytology Neurons/metabolism* RNA, Messenger/genetics RNA, Messenger/metabolism Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Subcellular Fractions Tissue Distribution