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Peroxisomal calcium handling and homeostasis

dc.contributor.advisorThoms, Sven Prof. Dr.
dc.contributor.authorSargsyan, Yelena
dc.titlePeroxisomal calcium handling and homeostasisde
dc.contributor.refereeThoms, Sven Prof. Dr.
dc.description.abstractengPeroxisomes are ubiquitous cellular organelles in eukaryotes essential for metabolism. The close localization of peroxisomes with the sarcoplasmic reticulum and T-tubules is known from electron micrographs of rodent hearts. This association of peroxisomes with sites of excitation-contraction coupling suggests a peroxisomal role in calcium handling. However, there is little known about peroxisomal calcium and previous studies brought up extensive contradictions. This work addresses peroxisomal Ca2+ handling in non-excitable HeLa cells, and in excitable cells represented by cardiomyocytes. Using both models, it is demonstrated that peroxisomal Ca2+ rises in dependance of cytosolic Ca2+ from a steady state of 600 nM to 2.4 µM. It is also shown that over 80% of peroxisomes in cardiomyocytes are in contact with ryanodine receptors and that cardiac peroxisomes take up Ca2+ when intracellular Ca2+ stores are depleted. These results suggest that peroxisomes in cardiomyocytes may contribute to an effective excitation-contraction process. Further, we studied the mechanisms of Ca2+ entry to peroxisomes. Taken together, this work provides the first evidence of peroxisomal Ca2+ handling taking place in cardiomyocytes and that several mechanisms to interact with it exist. Modulation of peroxisomal Ca2+ homeostasis may have future clinical application in cases of impaired cellular Ca2+ handling, such as certain types of
dc.contributor.coRefereeRizzoli, Silvio Prof. Dr.
dc.subject.engperoxisomes, calciumde
dc.affiliation.instituteMedizinische Fakultät
dc.subject.gokfullMedizin (PPN619874732)de

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