Mitochondrial dynamics and quality control in Huntington's disease

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• 作者：Pedro Guedes-Dias^a ; ^b ; Brí ; gida R. Pinho^a ; Tâ ; nia R. Soares^a ; Joã ; o de Proenç ; a^a ; Michael R. Duchen^b ; Jorge M.A. Oliveira^a ; ^{jorgemao@ff.up.pt" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ambra1 ; activating molecule in Beclin1-regulated autophagy 1 ; Atg ; autophagy-related protein ; BDNF ; brain-derived neurotrophic factor ; BNIP3 ; BCL2/adenovirus E1B 19&#xA0 ; kDa interacting protein 3 ; CREB ; cAMP response element-binding ; DIC ; dynein intermediate chain ; Drp1 ; dynamin-related protein 1 ; FEZ1 ; fasciculation and elongation protein zeta-1 ; Fis1 ; mitochondrial fission 1 protein ; GABARAPL1 ; GABA(A) receptor-associated protein like 1 ; HAP1 ; huntingtin-associated protein 1 ; HDAC ; Histone dea
• 刊名：Neurobiology of Disease
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：90
• 期：Complete
• 页码：51-57
• 全文大小：542 K

文摘

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD.