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Peroxisomal calcium handling and homeostasis

dc.contributor.advisorThoms, Sven Prof. Dr.
dc.contributor.authorSargsyan, Yelena
dc.date.accessioned2022-04-26T12:04:29Z
dc.date.available2024-01-20T00:51:14Z
dc.date.issued2022-04-26
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?ediss-11858/14012
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-9103
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc610
dc.titlePeroxisomal calcium handling and homeostasisde
dc.typedoctoralThesisde
dc.contributor.refereeThoms, Sven Prof. Dr.
dc.date.examination2022-01-21de
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 arrhythmias.de
dc.contributor.coRefereeRizzoli, Silvio Prof. Dr.
dc.subject.engperoxisomes, calciumde
dc.identifier.urnurn:nbn:de:gbv:7-ediss-14012-4
dc.affiliation.instituteMedizinische Fakultät
dc.subject.gokfullMedizin (PPN619874732)de
dc.description.embargoed2024-01-20de
dc.identifier.ppn1800458142


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