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Talk by Eric Herrmann

Title: "Overwhelmed organelles and frozen fibrils: A cryo-electron tomography study of organelle dysfunction in Parkinson’s disease "
Occasion: CRC -Seminar
Start: 30.10.2025, 16:15
Location: CellNanOs, 38/201

About the speaker: Dr. Eric Herrmann conducts research at the University of California, Berkeley, USA

Parkinson’s disease (PD) is a progressive neurodegenerative disorder driven in part by the accumulation of α- synuclein, a protein that aggregates into toxic oligomers and fibrils. These aggregates impair critical cellular organelles, particularly mitochondria and lysosomes, triggering mitochondrial depolarization, lysosomal membrane permeabilization, and ultimately the escape and propagation of α-synuclein aggregates to neighboring cells.

In this study, we apply cryo-electron tomography (cryo-ET) to capture these pathological changes at nanometer-scale resolution. As an initial step, we use pharmacological agents to simulate α-synuclein- induced damage and define baseline organelle phenotypes. We observe strong alterations in mitochondrial cristae architecture, shifts in protein localization, and resolve the human prohibitin complex in multiple conformational states. In lysosomes, we detect severe swelling, membrane remodeling, and active lysophagy.

Building on this, we are now introducing monomeric and preformed α-synuclein fibrils into primary neurons and rat astrocytes to directly observe disease-relevant organelle dysfunction and trace how these fibrils evade lysosomal degradation, offering insights into the cellular mechanisms of PD progression.