Mitophagy and long-term neuronal homeostasis

Neurons are highly polarized, post-mitotic cells that are characterized by unique morphological diversity and complexity. As highly differentiated cells that need to survive throughout organismal lifespan, neurons face exceptional energy challenges in time and space. Therefore, neurons are heavily dependent on a healthy mitochondrial network for their proper function and maintenance under both physiological and stress conditions. Multiple quality control systems have evolved to fine-tune mitochondrial number and quality, thus preserving neuronal energy homeostasis. Here, we review the contribution of mitophagy, a selective form of autophagy that targets dysfunctional or superfluous mitochondria for degradation, in maintaining nervous system homeostasis. In addition, we discuss recent evidence implicating defective or dysregulated mitophagy in the pathogenesis of neurodegenerative diseases.