Nuttall James M, Motley Alison M, Hettema Ewald H
Department of Molecular Biology and Biotechnology; University of Sheffield, Western Bank; Sheffield, UK.
Autophagy. 2014 May;10(5):835-45. doi: 10.4161/auto.28259. Epub 2014 Mar 18.
Turnover of damaged, dysfunctional, or excess organelles is critical to cellular homeostasis. We screened mutants disturbed in peroxisomal protein import, and found that a deficiency in the exportomer subunits Pex1, Pex6, and Pex15 results in enhanced turnover of peroxisomal membrane structures compared with other mutants. Strikingly, almost all peroxisomal membranes were associated with phagophore assembly sites in pex1Δ atg1Δ cells. Degradation depended on Atg11 and the pexophagy receptor Atg36, which mediates degradation of superfluous peroxisomes. Mutants of PEX1, PEX6, and PEX15 accumulate ubiquitinated receptors at the peroxisomal membrane. This accumulation has been suggested to trigger pexophagy in mammalian cells. We show by genetic analysis that preventing this accumulation does not abolish pexophagy in Saccharomyces cerevisiae. We find Atg36 is modified in pex1Δ cells even when Atg11 binding is prevented, suggesting Atg36 modification is an early event in the degradation of dysfunctional peroxisomal structures in pex1Δ cells via pexophagy.
受损、功能失调或多余的细胞器的周转对细胞内稳态至关重要。我们筛选了过氧化物酶体蛋白导入过程中受到干扰的突变体，发现与其他突变体相比，转运体亚基Pex1、Pex6和Pex15的缺陷导致过氧化物酶体膜结构的周转增强。令人惊讶的是，在pex1Δ atg1Δ细胞中，几乎所有过氧化物酶体膜都与吞噬泡组装位点相关。降解依赖于Atg11和过氧化物酶体自噬受体Atg36，Atg36介导多余过氧化物酶体的降解。PEX1、PEX6和PEX15的突变体在过氧化物酶体膜上积累泛素化受体。有人认为这种积累会触发哺乳动物细胞中的过氧化物酶体自噬。我们通过遗传分析表明，在酿酒酵母中，阻止这种积累并不会消除过氧化物酶体自噬。我们发现，即使阻止Atg11结合，Atg36在pex1Δ细胞中也会被修饰，这表明Atg36修饰是pex1Δ细胞中通过过氧化物酶体自噬降解功能失调的过氧化物酶体结构的早期事件。
