Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo

作者：Chinta Shankar J; Mallajosyula Jyothi K; Rane Anand; Andersen Julie K^*

来源：Neuroscience Letters, 2010, 486(3): 235-239.

DOI：10.1016/j.neulet.2010.09.061

• Alpha-synuclein (alpha-syn)
• Mitochondria
• Oligomers
• Parkinson s disease
• Proteasomal inhibition
• Mitochondrial complex I (CI) activity
• Mitophagy

Alpha-synuclein is the major protein component of Lewy bodies a cardinal pathological feature of the degenerating Parkinsonian brain Alpha-synuclein has been reported to be able to intercalate Into membranes via formation of an alpha-helical structure at its N-terminal end Recent in vitro studies from various laboratories have demonstrated that alpha-synuclein can physically associate with mitochondria and interfere with mitochondrial function alpha-Syn predominantly associates with the Inner mitochondrial membrane where it can apparently Interact with complex I resulting in reduced mitochondrial complex I activity and increased free radical production However the effect of in vivo alpha-synuclein accumulation within dopaminergic neurons on mitochondrial function has not been thoroughly studied Examination of transgenic animals which overexpress the familial mutant A53T form of the protein selectively within dopaminergic neurons reveals that A53T localizes to the mitochondrial membranes as monomers and oligomers particularly under conditions of proteasomal inhibitory stress and that this localization coincides with a selective a

• 出版日期2010-12-17