Abstract: Damaged mitochondria are removed from the cell via mitophagy. This pathway may be important for neuronal homeostasis, as mutations in pathway components cause PD and ALS. We used live imaging to investigate the spatiotemporal dynamics of mitophagy in primary neurons following mild oxidative stress. Mitophagy-associated proteins rapidly translocate to depolarized mitochondria and mitochondria were sequestered in autophagosomes within an hour of damage. Surprisingly, the downstream degradation of engulfed mitochondria was delayed, primarily due to slow acidification of the resulting mitophagosomes. Expression of an ALS-associated mutation disrupted mitochondrial network function, and stress exacerbated this effect. These results suggest that slow turnover of damaged mitochondria may increase neuronal susceptibility to neurodegeneration.
About Dr. Evans:
Chantell Evans received her Ph.D. in Molecular and Cellular Pharmacology from the University of Wisconsin and is now a Postdoctoral Fellow at the University of Pennsylvania, where she uses advanced microscopy and biochemical techniques to gain insight into the molecular mechanisms that regulate mitophagy in primary neurons. She is particularly interested in examining mitochondrial quality control pathways in neurons and the role of mitochondrial regulation in neurodegenerative diseases.