P21-activated kinase 1 (PAK1) Regulates Autophagy in Human Cardiomyocytes

P21-activated kinase 1 (PAK1) is a serine/threonine protein kinase that plays a critical role in protecting cardiomyocytes, particularly under stress conditions. Autophagy, a lysosomal degradation pathway, is essential for breaking down cellular components and maintaining cellular integrity. While previous studies in rodent models have demonstrated that PAK1 regulates autophagy in cardiomyocytes, its role in human cells remains unexplored. In this study, we investigated the role of PAK1 in regulating autophagy flux in a human cardiomyocyte cell line (AC16) derived from human ventricular heart tissues. PAK1 was overexpressed in AC16 cells via adenovirus-mediated gene transfer, and autophagy flux was assessed by measuring LC3-II (microtubule-associated protein 1 light chain 3 form II) protein levels via western blotting, both with and without the addition of lysosomal protease inhibitors Pepstatin A (pepA) and Aloxistatin (E64d). PAK1 overexpression led to increased LC3-II levels, which were further elevated in the presence of pepA and E64d, suggesting that PAK1 enhances autophagosome production and accelerates autophagy flux. These findings indicate that PAK1 is a positive regulator of autophagy. Future studies will examine whether PAK1 knockdown affects autophagy activity and further investigate the molecular mechanisms by which PAK1 controls autophagy. NIH 1R15HL163707-01A1 (QL) NIH 1R15HL161737-01 (SK) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.