Mitochondrial Autophagy in Brain

Selective turnover of defective or worn-out mitochondria via autophagy is essential for maintaining a healthy mitochondrial network under both physiological and pathological conditions. This is important, especially in tissue with high-energy demand, such as the brain. As part of this chapter, we will give an update on mitochondrial autophagy with a focus on the PINK1–PRKN mitophagy pathway, which has been extensively studied since its discovery more than a decade ago. The rather low levels of patho−/physiological PINK1–PRKN signaling that occur in vivo and the general dynamic nature of mitophagy make it challenging to study. In addition to sensitive biochemical measurements, transgenic reporter mice that are available now allow analyses of mitophagy rates in a tissue-specific manner at baseline and under stress. We further describe the current status of knowledge on neuronal mitophagy and summarize findings in rodent models. A special emphasis is further placed on mitophagy in human neurological disorders including Parkinson’s disease and Alzheimer’s disease and the connection between defective mitophagy and neuroinflammation. The chapter concludes with current challenges and future therapeutic approaches to modulate mitophagy.