Peroxisomal calcium handling and homeostasis

by Yelena Sargsyan
Doctoral thesis
Date of Examination:2022-01-21
Date of issue:2022-04-26
Advisor:Prof. Dr. Sven Thoms
Referee:Prof. Dr. Sven Thoms
Referee:Prof. Dr. Silvio Rizzoli
Persistent Address: http://dx.doi.org/10.53846/goediss-9103

 

 

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Abstract

English

Peroxisomes 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.
Keywords: peroxisomes, calcium