ジャーナル: Mol Cell / 年: 2024 タイトル: Autophagy preferentially degrades non-fibrillar polyQ aggregates. 著者: Dorothy Y Zhao / Felix J B Bäuerlein / Itika Saha / F Ulrich Hartl / Wolfgang Baumeister / Florian Wilfling / 要旨: Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease ...Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease (HD). Huntingtin (Htt), the disease protein of HD, forms amyloid-like fibrils by liquid-to-solid phase transition. Macroautophagy has been proposed to clear polyQ aggregates, but the efficiency of aggrephagy is limited. Here, we used cryo-electron tomography to visualize the interactions of autophagosomes with polyQ aggregates in cultured cells in situ. We found that an amorphous aggregate phase exists next to the radially organized polyQ fibrils. Autophagosomes preferentially engulfed this amorphous material, mediated by interactions between the autophagy receptor p62/SQSTM1 and the non-fibrillar aggregate surface. In contrast, amyloid fibrils excluded p62 and evaded clearance, resulting in trapping of autophagic structures. These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.
集束イオンビーム - 装置: OTHER / 集束イオンビーム - イオン: OTHER / 集束イオンビーム - 電圧: 30 / 集束イオンビーム - 電流: 0.05 / 集束イオンビーム - 時間: 1800 / 集束イオンビーム - 温度: 100 K / 集束イオンビーム - Initial thickness: 1000 / 集束イオンビーム - 最終 厚さ: 250 集束イオンビーム - 詳細: The value given for _em_focused_ion_beam.instrument is FEI FIB. This is not in a list of allowed values {'OTHER', 'DB235'} so OTHER is written into the XML file.
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電子顕微鏡法
顕微鏡
FEI POLARA 300
撮影
フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 2.0 e/Å2