Mitophagy is the sole mechanism for neurons to eliminate superfluous or damaged mitochondria. Although the critical implications of mitophagy have been emphasized in a variety of
neurological disorders, it remains ambiguous how neurons control the quality of axonal mitochondria. By employing an
oxygen-
glucose-deprivation and reperfusion (OGD-Rep) model in cultured neurons, our recent results clearly documented the prompt recovery of retrograde transport of axonal mitochondria to neuronal
soma. Moreover, by selectively labeling axonal mitochondria, we found that these axonal mitochondria appear in neuronal
soma and are eliminated via autophagosomes in priority. This mitochondrial movement from axon to
soma has a critical contribution to overall neuronal mitophagy under
ischemia. Because forced expression of an anchoring
protein, SNPH (Syntaphilin), significantly blocks mitophagy, and aggravates
mitochondrial dysfunction and neuronal injury. Conversely, promoted retrograde mitochondrial movement facilitates neuronal mitophagy and attenuates ischemic neuronal demise. In conclusion, we propose stimulating the somatic autophagy of axonal mitochondria after ischemic insults. These findings may provide further insight into how neurons control the mitochondrial quality in pathological conditions and offer novel strategies to cure
neurological disorders.