Fass Ephraim, Shvets Elena, Degani Ilan, Hirschberg Koret, Elazar Zvulun
Department of Biological Chemistry and Chemical Physics, Weizmann Institute of Science, Rehovot, 76100, Israel.
J Biol Chem. 2006 Nov 24;281(47):36303-16. doi: 10.1074/jbc.M607031200. Epub 2006 Sep 8.
Autophagy is a major catabolic pathway in eukaryotic cells whereby the lack of amino acids induces the formation of autophagosomes, double-bilayer membrane vesicles that mediate delivery of cytosolic proteins and organelles for lysosomal degradation. The biogenesis and turnover of autophagosomes in mammalian cells as well as the molecular mechanisms underlying induction of autophagy and trafficking of these vesicles are poorly understood. Here we utilized different autophagic markers to determine the involvement of microtubules in the autophagic process. We show that autophagosomes associate with microtubules and concentrate near the microtubule-organizing center. Moreover, we demonstrate that autophagosomes, but not phagophores, move along these tracks en route for degradation. Disruption of microtubules leads to a significant reduction in the number of mature autophagosomes but does not affect their life span or their fusion with lysosomes. We propose that microtubules serve to deliver only mature autophagosomes for degradation, thus providing a spatial barrier between phagophores and lysosomes.
自噬是真核细胞中的主要分解代谢途径,氨基酸缺乏会诱导自噬体的形成,自噬体是一种双层膜囊泡,介导胞质蛋白和细胞器向溶酶体的运输以便进行降解。哺乳动物细胞中自噬体的生物发生和周转,以及自噬诱导和这些囊泡运输的分子机制仍知之甚少。在这里,我们利用不同的自噬标记物来确定微管在自噬过程中的作用。我们发现自噬体与微管相关联,并集中在微管组织中心附近。此外,我们证明自噬体而非吞噬泡沿着这些轨道移动以进行降解。微管的破坏导致成熟自噬体数量显著减少,但不影响其寿命或与溶酶体的融合。我们认为微管仅用于运输成熟自噬体进行降解,从而在吞噬泡和溶酶体之间提供了一个空间屏障。