Quality Control in Neurons: Mitophagy and Other Selective Autophagy Mechanisms.
The cargo-specific removal of organelles via selective autophagy is important to maintain neuronal homeostasis. Genetic studies indicate that deficits in these pathways are implicated in neurodegenerative diseases, including Parkinson's and amyotrophic lateral sclerosis. Here, we review our current understanding of the pathways that regulate mitochondrial quality control, and compare these mechanisms to those regulating turnover of the endoplasmic reticulum and the clearance of protein aggregates. Research suggests that there are multiple mechanisms regulating the degradation of specific cargos, such as dysfunctional organelles and protein aggregates. These mechanisms are critical for neuronal health, as neurons are uniquely vulnerable to impairment in organelle quality control pathways due to their morphology, size, polarity, and postmitotic nature. We highlight the consequences of dysregulation of selective autophagy in neurons and discuss current challenges in correlating noncongruent findings from in vitro and in vivo systems.
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