Uttenweiler Andreas, Schwarz Heinz, Neumann Heinz, Mayer Andreas
Département de Biochimie, Université de Lausanne, 1066 Epalinges, Switzerland.
Mol Biol Cell. 2007 Jan;18(1):166-75. doi: 10.1091/mbc.e06-08-0664. Epub 2006 Nov 1.
Microautophagy involves direct invagination and fission of the vacuolar/lysosomal membrane under nutrient limitation. This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. In this study we have identified the VTC (vacuolar transporter chaperone) complex as required for microautophagy. The VTC complex is present on the ER and vacuoles and at the cell periphery. On induction of autophagy by nutrient limitation the VTC complex is recruited to and concentrated on vacuoles. The VTC complex is inhomogeneously distributed within the vacuolar membranes, showing an enrichment on autophagic tubes. Deletion of the VTC complex blocks microautophagic uptake into vacuoles. The mutants still form autophagic tubes but the production of microautophagic vesicles from their tips is impaired. In line with this, affinity-purified antibodies to the Vtc proteins inhibit microautophagic uptake in a reconstituted system in vitro. Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes.
微自噬涉及在营养限制条件下液泡/溶酶体膜的直接内陷和分裂。这是通过自噬管发生的,自噬管是一种特殊的液泡膜内陷结构,它将囊泡 pinched off 到液泡腔中。在本研究中,我们已确定VTC(液泡转运伴侣)复合体是微自噬所必需的。VTC复合体存在于内质网、液泡以及细胞周边。在营养限制诱导自噬时,VTC复合体被招募到液泡并集中在液泡上。VTC复合体在液泡膜内分布不均,在自噬管上有富集。VTC复合体的缺失会阻断微自噬进入液泡的过程。突变体仍会形成自噬管,但从其顶端产生微自噬囊泡的过程受到损害。与此一致的是,针对Vtc蛋白的亲和纯化抗体在体外重组系统中会抑制微自噬摄取。我们的数据表明,VTC复合体是自噬管的重要组成部分,并且它是微自噬囊泡从这些管子上分裂所必需的。 (注:原文中“pinches off”直译为“掐断”,这里意译为“分离出”更符合语境;“scission”直译为“分裂”,这里意译为“分离”更符合语境)