Mitochondria is no longer viewed as merely a powerhouse of the cell. It is now apparentthat mitochondria play a central role in signaling, maintaining cellular homeostasis and cell fate.Mitochondrial dysfunction has been linked to many human diseases caused by cellular metabolicderegulation, such as obesity, diabetes, neurodegenerative disease, cardiovascular disease andcancer. Eukaryotic organisms have evolved an efficient way in sensing, communicating andresponding to cellular stress and regulating mitochondrial activity correspondingly through acomplex network of intercommunicating protein kinases and their downstream effectors. Thisdissertation focuses on the interplay of two of the master metabolic regulators in the cell: AMPKand PASK, and characterization of the functions of their downstream substrates: OSBP andMED13. AMPK is an energy sensing kinase that maintains energy homeostasis in the cell,whereas PASK is a nutrient sensing kinase that regulates glucose partitioning and respiration inthe cell. Both kinases play important roles in mitochondrial function and regulation, anddeficiency in either kinase has been found to associate with various human pathologies. Furthercharacterization of the cross-talk and molecular mechanisms of both kinases in controllingmitochondrial health and function may aid in the identification of new targets for treatingmetabolic diseases.
College and Department
Life Sciences; Microbiology and Molecular Biology
BYU ScholarsArchive Citation
Ong, Kai Li, "SNFing Glucose to PASs Mitochondrial Dysfunction: The Role of Two Sensory Protein Kinases in Metabolic Diseases" (2019). Theses and Dissertations. 8587.
AMP-activated Kinase; SNF1; Oxysterol binding protein; OSBP; Osh6; Osh7;, ORP5; ORP8; PAS Kinase; Med13; cyclin C; mitochondria function; mitochondria dynamic;, mitophagy