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GDCB Seminar — “Understanding peroxisomal stress responses”

Oct 16, 2020 - 4:00 PM
to Oct 16, 2020 - 5:00 PM
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Hua Bai, GDCB assistant professorSpeaker: Hua Bai, assistant professor in the Iowa State University Department of Genetics, Development and Cell Biology

Title: “Understanding peroxisomal stress responses”

Abstract: “Peroxisomes are essential and yet least studied subcellular organelles of all eukaryotic cells. They play crucial roles in the regulation of cellular redox homeostasis, oxidation of very long chain fatty acids (VLCFAs), and biosynthesis of ether phospholipid. Because most of the peroxisomal matrix proteins are synthesized in the cytosol, all peroxisomal functions are dependent on the import of matrix proteins into the organelle. Disrupted peroxisomal import often leads to severe impairment of tissue functions and animal aging. Despite the indispensable role of peroxisomes in cellular and metabolic homeostasis, our knowledge on how cells cope with peroxisome dysfunction and impaired peroxisomal import is largely missing. We have recently performed genomics and genetic analyses to map the key components in peroxisomal stress response pathways. About 2600 candidate genes were identified through a pooled genome-wide CRISPR screening in human embryonic kidney cells (HEK293), and knockdown of these candidate genes either improved or reduced cell fitness upon peroxisomal stress. Genes involved in Hippo, MAPK, and splicing pathways are enriched. Interestingly, a serine/arginine-rich pre-mRNA splicing factor SCAF1 was identified among the top candidate genes. Knockdown of SCAF1 significantly attenuated peroxisomal stress-induced phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α), a hallmark of the integrated stress response and translation inhibition. Consequently, cells with SCAF1 KD showed increased caspase 3 activities and apoptosis. Thus, our studies identified a novel splicing factor that is involved in cytoprotective responses and translation inhibition during peroxisomal stress.”

Link: https://iastate.webex.com/iastate/j.php?MTID=m552722056e5078dee22caa75af9541f1