MEC17 Induced α‐tubulin Acetylation Restores Mitochondrial Transport Function and Alleviates Axonal Injury after Intracerebral Hemorrhage in Mice

AbstractInjury to long axonal projections is a central pathological feature at the early phase of intracerebral hemorrhage (ICH). It has been reported to contribute to persistent functional disability following ICH. However, the molecular mechanisms that drive axonal degeneration remain unclear. Autologous blood was injected into the striatum to mimic the pathology of ICH. Observed significant swollen axons with characteristic retraction bulbs were found around the striatal hematoma at 24h after ICH. Electronic microscopic examination revealed highly disorganized microtubule and swollen mitochondria in the retraction bulbs. MEC17 is a specific α-tubulin acetyltransferase, ablation of acetylated α-tubulin inMEC17-/- mice aggravated axonal injury, axonal transport mitochondria dysfunction and motor dysfunction. In contrast, treatment with Tubastatin A (TubA), which promotes microtubule acetylation, significantly alleviated axonal injury and protected the integrity of corticospinal tract and fine motor function after ICH. Moreover, results showed that 41% mitochondria were preferentially bundled to the acetylated α-tubulin in identifiable axons and dendrites in primary neurons. This impaired axonal transport of mitochondria in primary neurons ofMEC17-/- mice. Given that opening of mitochondrial permeability transition pore (mPTP) induces mitochondrial dysfunction and impairs ATP supply thereby promoting axonal injury, we enhanced the availability of acetylated α-tubulin usin...

Source: Journal of Neurochemistry - August 18, 2021 Category: Neuroscience Authors: Yang Yang, Xuezhu Chen, Zhizhong Feng, Xianfeng Cai, Xiaoming Zhu, Ming Cao, Likun Yang, Yujie Chen, Yuhai Wang, Hua Feng Tags: ORIGINAL ARTICLE Source Type: research