Publication

Mitochondrial function in cardiomyocytes

Tigchelaar, W., 2017, [Groningen]: Rijksuniversiteit Groningen. 207 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Wardit Tigchelaar
Cardiac remodeling underlies heart failure development, which is a major public health problem and is associated with high morbidity and mortality. Cardiomyocyte hypertrophy (growth) is one of the hallmarks of cardiac remodeling. There is increasing awareness, that changes in mitochondria, the main energy producing organelles in the cell, may play a role in pathological hypertrophy development.
We investigated the role of several mitochondrial proteins in relation to mitochondrial function and hypertrophy in a cell culture model of rat neonatal cardiomyocytes. In particular we investigated mitochondrial localized AKIP1 and EXOG, which were identified in genetic screens for hypertrophy associated genes. We could show that altered expression levels of these proteins increased mitochondrial respiration and induced hypertrophy. In AKIP1 overexpressing cells a more efficient mitochondrial respiration was observed with less reactive oxygen species (ROS) production. In contrast, in EXOG depleted cells the induced cardiomyocyte hypertrophy was partially dependent on increased mitochondrial ROS. Thus, both mitochondrial ROS dependent and independent mechanisms can trigger hypertrophy. Our studies also revealed a role for the motor protein Kif5B in mitochondrial localization in cardiomyocytes. Pathological hypertrophy increased Kif5b levels and this affected mitochondrial localization and function. Reduction of Kif5B levels resulted in a partial normalization of mitochondrial activity and diminished cardiomyocyte hypertrophy. Thus, mitochondrial distribution in cardiomyocytes is relevant to mitochondrial function and alterations are related to pathological hypertrophy.
In summary, we identified new components controlling mitochondrial function and hypertrophy in cultured cardiomyocytes. Altered mitochondrial function can stimulate hypertrophy and could potentially be an interesting therapeutic target.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date3-Jul-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9870-9
Electronic ISBNs978-90-367-9869-3
Publication statusPublished - 2017

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