WEHI Parkinson’s Disease Special Seminar hosted by Michael Lazarou and Runa Lindblom
Erika L.F. Holzbaur Perelman School of Medicine, University of Pennslyvania, USA
Organelle quality control in neuronal homeostasis and neurodegeneration
Davis Auditorium (speaker online) Join via ZOOM Webinar ID: 810 7863 9963 Passcode: 113339 Including Q&A session
Organelle quality control pathways are central to the maintenance of cellular homeostasis. Acute damage to organelles can induce cellular response mechanisms leading to organelle repair or to organelle turnover, with selective autophagy as the major pathway driving removal. Phase condensate dynamics have been implicated in the regulation of multiple aspects of the selective autophagy of lysosomes and mitochondria. I will discuss our recent progress in understanding the formation of phase condensates following organelle damage, how the fluidity of these phase condensates is modulated by upstream signaling pathways and downstream effectors, and the cellular effects of alterations in phase condensate behavior during selective autophagy. Specifically, we find that the fluidity of p62/SQSTM1 phase condensates formed in response to lysosomal damage is modulated by the small heat shock protein HSP27; the fluidity of these condensates is critical in the clearance of damaged lysosomes via lysophagy. We also see the formation of phase condensates of p62 on damaged mitochondria during mitophagy. In this context, however, we find that p62-positive condensates mediate the assembly of NEMO into a signaling platform that activates proinflammatory NF-kB signaling. Thus, phase condensates regulate both organelle turnover and cellular responses to organelle damage.
Erika L. F. Holzbaur is the William Maul Measey Professor of Physiology at the University of Pennsylvania Perelman School of Medicine. She received her B.S. with High Honors in Chemistry and History from the College of William and Mary and her PhD in Biochemistry from Penn State. Holzbaur joined the faculty at Penn in 1992, where she is now holds an endowed professorship in the Department of Physiology. The Holzbaur lab studies the dynamics of organelle trafficking in neurons. Organelles including mitochondria, autophagosomes, and lysosomes are actively transported over distances of a meter or more along the axons and dendrites of neurons; defects in this trafficking are causative for both neurodevelopmental and neurodegenerative disease. The lab also investigates cellular mechanisms required to maintain neuronal homeostasis, focusing on the dynamics of autophagy and mitophagy. Defects in these pathways lead to the accumulation of dysfunctional organelles and aggregated proteins, and are implicated in both Parkinson’s disease and ALS. Dr. Holzbaur has received a Porter Fellowship, the NINDS Javits Award, the Stanley N. Cohen Biomedical Research Award, the Jane M. Glick Graduate Student Teaching Award, the Sandra K. Masur Senior Leadership Award, and is a Lifetime Fellow and past President of the American Society for Cell Biology. More than 40 postdocs and students have trained in her lab, many now running research labs at top universities in the US and internationally.