p62/SQSTM1-Dependent Autophagy of Lewy Body-Like α-Synuclein Inclusions

• DOI: 10.1371/journal.pone.0052868
• Publication Date: 2012-12-31T22:26:19Z
• Authors: Yoshihisa Watanabe; Harutsugu Tatebe; Katsutoshi Taguchi; Yasuhisa Endo; Takahiko Tokuda; Toshiki Mizuno; Masanori Nakagawa; Masaki Tanaka
• Keywords: Bafilomycin; HEK 293 cells; Lewy body; Inclusion bodies; Sequestosome 1

α-Synuclein is the main component of Lewy bodies, intraneuronal inclusion bodies characteristic Parkinson's disease. Although α-synuclein accumulation caused by inhibition proteasome and autophagy-lysosome, degradation inclusions still unknown. Formation body-like can be replicated in cultured cells introducing fibrils generated vitro. We used this cell culture model to investigate autophagy impaired mitochondria. The intracellular immediately underwent phosphorylation ubiquitination. Simultaneously they were encircled an adaptor protein p62/SQSTM1 directed autophagy-lysosome pathway HEK293 line. Most phospho-α-synuclein-positive degraded 24 h, however, lysosomal dysfunction with bafilomycin A1 significantly affected their clearance. Moreover, Atg-5 siRNA treatment reduced incorporation into LC3-positive autophagosomes. Knockdown experiments demonstrated requirement p62 for autophagy. These results demonstrate that are preferred targets p62-dependent Next, we investigated autophagic clearance mitochondria inclusion-containing cells. Impaired almost completely eliminated after mitochondrial uncoupling even presence inclusions, suggesting not prevented