Tens of millions of people suffer from cerebral ischemia worldwide，whereas unfortunately, limited clinical approaches are available in the current stage due to the extremely complicated pathological mechanisms of ischemic injury and a lack of precise therapeutic targets.
Neuronal death induced by the sudden shortage of blood supply is one of the major outcomes of cerebral ischemia. Neurons serve as a “commander” of whole body, whose dysfunctionsresult in failures in controlling basic physiological functions and even death. Neurons are also distinguished from other cells by its unique morphology consisting of a cell body (soma), numerous dendrites and a long, thin axon. Like a highway for information, axon transmits information and conveys “commands” from neuron at every moment, which is fueled by cellular powerhouse, mitochondria.Since damaged mitochondria produce energy less efficiently and may induce neuronal demise, mitochondrial control quality is critical for neuronal health and functions. Neurons monitor mitochondrial quality mainly by eliminating dysfunctional mitochondria through autophagy–lysosomal system (mitophagy). however, how axonal mitochondria are cleared is not fully understood.
On April 12, 2019, Prof. Zhong Chen’s group from Zhejiang University in China published a research article entitled “Somatic autophagy of axonal mitochondria in ischemic neurons” in Journal of Cell Biology, uncovering novel features of mitophagy in ischemic neurons.Prof. Zhong Chen’s group has previously shown that mitophagy activated by ischemia-reperfusion protects against cerebral ischemic injury (Autophagy, 2013; 2014; 2017a; 2017b). Thus, further investigations into the mechanisms of mitophagy, especially in ischemic neurons, are needed for novel strategies against cerebral ischemia. Here, Prof. Zhong Chen’s research group proves that axonal mitochondrial is cleared by somatic but not local mitophagy in ischemic neurons. These axonal mitochondria were retrogradely transported back to neuronal cell bodies for degradation. Reinforced retrograde transport of axonal mitochondria promoted mitophagy and attenuated mitochondrial dysfunction and ischemic neuronal injury. These spatial features of mitophagy provide insight into how neurons control mitochondrial quality under pathological conditions and this study proposes a new concept that to reduce ischemic neuronal injury by correcting mitochondrial motility.
This work was funded by the National Natural Science Foundation of China. Graduate students Yanrong Zheng and Xiaoli Wu from college of pharmaceutical sciences, Zhejiang University are co-first authors of this article. Prof. Xiangnan Zhang from college of pharmaceutical sciences, Zhejiang University is the co-corresponding author as well as co-first author.
The paper linker:http://jcb.rupress.org/content/early/2019/04/11/jcb.201804101.long