Mitochondria, two membrane organelles, located
in the cytoplasm of eukaryotic cells are
responsible for the most important processes of the cell, tissue and even the whole organism.
The small factories produce energy, maintain the calcium homeostasis, control the redox
potential and are involved in many metabolic and biosynthetic pathways. Additionally,
mitochondria perform heat production by dissipation of the proton gradient. This specific
activity is done in brown adipose tissue (BAT) by a protein located in the inner mitochondrial
membrane. This protein is called thermogenin (Uncoupling protein 1) and is responsible for the non-shivering thermogenesis. UCP1 belongs to the subfamily of uncoupling proteins inside a mitochondrial anion carrier family. The study of the uncoupling proteins, their function and regulation, as well as their involvement in the pathogenesis of various diseases is an important part of current basic research. In the present work, the expression pattern of the members of the uncoupling protein family is analysed under different conditions. Recent
discoveries show an association between the uncoupling proteins and civilization diseases
such as obesity, type II diabetes, ischemia, cancer and neurodegenerative diseases. Meanwhile
function and localization of UCP1 are well studied, the functions and tissue distributions of
the four other members remain unknown or disputed. The absence of the characteristic
phenotype in knockout mice (UCP1-/ -, UCP2-/ -, UCP3-/ -) could be explained by taking over the function of the ablated protein by the remaining sister protein(s). This hypothesis of compensatory expression is based on the high homology between the members (30 to 75%).
In the presented work we studied the expression patterns of UCP1-UCP5 in UCP1-/-, UCP2-/-,UCP3-/- and wild type mice under physiological conditions. We examined the tissue distribution of UCP1-UCP5 with evaluated antibodies. On one hand, our results refute the hypothesis of a possible compensatory role of UCP proteins for each other. But on the other hand the strong variability of their expression (UCP2, UCP3), even under physiological conditions could be shown. The two proteins, UCP2 and UCP3, were previously described to be regulated at the translational level. We have observed that the knockout of UCP1 decreases the amount of UCP3 in brown adipose tissue significantly. We assume that UCP3 in BAT has a different function which is not related to the function, of UCP1 and UCP2. Changing the parameters of the surrounding environment as temperature, humidity and also changing of the physiological conditions, such as physical activity and diet (high fat diet, high sugar diet, caloric restriction and food deprivation) of the UCP1-/-, UCP2-/-, UCP3-/- will be necessary for further investigation of the UCP function.
The analysis of knockout mice under various conditions and requirements will lead to the elucidation of UCP function and explain their role in health and disease.