Student Presenter(s): Peter Girgis, Anoushka Guha, Pooja Jaiswal
Faculty Mentor: Satoru Kobayashi
Department: Biomedical Science
School/College: College of Arts and Sciences, Long Island

P21-activated serine/threonine Kinase 1 (PAK1) plays an integral role in the homeostasis of cardiac muscle cells (cardiomyocytes). Autophagy is a process that helps maintain cellular homeostasis by removing and recycling injured and obsolete intracellular components. Mitophagy is a form of selective autophagy that eliminates injured mitochondria. In previous studies, we have demonstrated that PAK1 is essential and sufficient to maintain both autophagy and mitophagy. However, the downstream pathways of PAK1-dependent autophagy and mitophagy remain unclear. In this study, we seek to identify the effectors that mediate the ability of PAK1 to regulate autophagy and mitophagy. The H9c2 cardiac myoblast cells were treated with siRNA to knockdown PAK1, and the protein expression levels of important regulators were determined with Western blot analyses. The ATG5-12 complex is an essential promoter of autophagosome formation. TFEB is a master transcription factor that regulates the expressions of autophagy and lysosome genes. p62 is an adaptor and receptor for cellular components that are marked for degradation by autophagy. Our results showed that PAK1 knockdown reduced the protein expression levels of all the above factors, which are expected to attenuate autophagy activities. In addition, PAK1 knockdown also diminished the expression of FUNDC1, a mitophagy receptor essential for mitophagy. These results may explain why PAK1 is able to positively regulate autophagy and mitophagy.