Inhibition of mitochondrial protein import by mutant huntingtin

摘要: Mitochondrial dysfunction is associated with neuronal loss in Huntington’s disease (HD), a neurodegenerative caused by an abnormal polyglutamine expansion huntingtin (Htt). However, the mechanisms linking mutant Htt and mitochondrial HD remain unknown. We identify interaction between TIM23 protein import complex. Remarkably, recombinant directly inhibited vitro. Furthermore, mitochondria from brain synaptosomes of presymptomatic model mice Htt-expressing primary neurons exhibited defect, suggesting that deficient early event HD. The Htt–induced defect subsequent death were attenuated overexpression complex subunits, demonstrating causes Htt-induced death. Collectively, these findings provide evidence for direct link Htt, pathology, implications import–based therapies