Mitochondria power neuronal axon growth and regeneration

2017

Challenge

Cellular structures called mitochondria power neuron growth, survival, and function. Due to their extended axons, the long thread-like part of a nerve cell, neurons face the unique challenge of maintaining mitochondrial distribution to provide sufficient energy production in regions where energy demand is high. However, it remains unclear exactly how the distribution of mitochondria in neurons is altered by changes in energy needs, stress, or injury.

Advance

IRP investigators, led by Zu-Hang Sheng, Ph.D., discovered that nerve injury severely damages mitochondria and their movement along neurons. Moreover, the increased energy required for regenerating produces a local energy crisis in injured axons, which severely decreases the axons’ ability to regrow after injury. However, Dr. Sheng’s team found that genetically ‘boosting’ the transport of mitochondria along the axons of nerve cells helps remove damaged mitochondria and supplies healthy ones to injured axons, thus rescuing the nerve from an injury-induced energy crisis and enhancing the ability of nerve cells to repair themselves after injury.

Impact

These findings revealed that maintaining an adequate energy supply in axons is crucial to meeting the increased energy demands of nerve regeneration after injury. In addition, the discoveries point towards novel therapeutic strategies for increasing the regeneration of neurons after injury by enhancing local mitochondrial transport or boosting mitochondrial energy production.  

Publications

Lin MY, Cheng XT, Tammineni P, Xie Y, Zhou P, Cai Q, Sheng ZH. (2017). Releasing syntaphilin removes stressed mitochondria from axons independent of mitophagy under pathophysiological conditions. Neuron. 94(3):595-610.

Zhou B, Yu P, Lin MY, Sun T, Chen Y, Sheng ZH. (2016). Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits. Journal of Cell Biology. 214(1):203-119.

Xie Y, Zhou B, Lin MY, Wang S, Foust KD, Sheng ZH. (2015). Endolysosome deficits augment mitochondria pathology in spinal motor neurons of asymptomatic fALS-linked mice. Neuron. 87(2):355-370.