Brown adipocytes mitochondria-peorxisomes crosstalk through catalase and MnSOS redistribution hypothyroidism

Abstract

Mitochondria and peroxisomes are highly dynamic organelles which cooperate and cross-talk in the cell. They are metabolically linked through fatty acids, where peroxisomes, as mitochondrial partner organelles, oxidise long and branched fatty acids. It is well established that metabolism in hypothyroidism, lipid metabolism in particular, is changed. As a consequence of that, peroxisomes take over the main role in β-oxidation of fatty acids. Hence, the aim of our study was to examine protein expression, activity and cell localisation of peroxisomal and mitochondrial enzymes − catalase (CAT) and manganese superoxide dismutase (MnSOD), in rat brown adipose tissue. Two month old male Wistar rats were fed with standard pelleted food ad libitum. Hypothyroidism was induced with 0.04% methimazole given in drinking water for 7, 15, 21 days respectively; control animals drank tap water. An isolated portion of interscapular brown adipose tissue was examined by: western blot, enzymatic activity assay, immunohistochemistry and immunocytochemistry. Our results show that the treatment increased protein expression of both CAT and MnSOD. Enzymatic activity of CAT was increased during the treatment. In contrast, MnSOD enzymatic activity was slightly increased to the 15th day of the treatment and then significantly decreased. Subcellular localization showed CAT presence in all cell compartments: cytoplasm, nucleus, mitochondria, peroxisomes and around lipid droplets. Also, the number of CAT-immunopositive cells was increased during the treatment. MnSOD was localised in mitochondria and peroxisomes adjacent to lipid droplets. Ultrastructural analysis showed remarkable MnSOD localisation in peroxisomes in experimental groups. The intensity of MnSOD immunopositivity was also increased in experimental groups, especially in the group treated for 15 days. Moreover, we found the harlequin pattern of immunostaining for both enzymes was potentiated in hypothyroidism. The lack of thyroid hormones alters mitochondria-peroxisomes crosstalk through increase in peroxisomes number, catalase expression and catalase activity, but also via catalase and MnSOD organellar redistribution in brown adipocytes.