Membrane recruitment of Atg8 by Hfl1 facilitates turnover of vacuolar membrane proteins in yeast cells approaching stationary phase.
Membrane recruitment of Atg8 by Hfl1 facilitates turnover of vacuolar membrane proteins in yeast cells approaching stationary phase.
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Hfl1 对 Atg8 的膜募集促进接近稳定期的酵母细胞中液泡膜蛋白的周转
DOI：
10.1186/s12915-021-01048-7
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发表时间：
2021-06-04
期刊：
影响因子：
5.4
通讯作者：
Xie Z
中科院分区：
文献类型：
--
作者：
He CW;Cui XF;Ma SJ;Xu Q;Ran YP;Chen WZ;Mu JX;Li H;Zhu J;Gong Q;Xie Z
背景液泡/溶酶体是自噬途径的最终目的地，但本身也可以被选择性的大自噬或微自噬过程全部或部分降解。在这些过程中涉及不同的分子机制，其表征落后于依赖ATG的巨型自噬和依赖ESCRT的内体多囊体途径。结果我们发现，随着酵母细胞逐渐耗尽有效营养并接近稳定期，多个功能无关的空泡完整膜蛋白在液泡腔中被降解。这种降解依赖于ESCRT机制，但并不严格要求将货物泛素化或将货物运出液泡。它在时间和机制上也不同于鼻咽癌依赖的微脂吞噬。ATG8是自噬蛋白中的一个例外，它和一种与ATG8相互作用的液泡膜蛋白Hfl1促进了自噬的转换。ATG8或Hfl1的缺失导致液泡内腔膜结构的增大。我们进一步证明，Hfl1的一个关键功能是Atg8的膜募集。在Hfl1存在的情况下，Atg8的脂化不需要有效的货物周转。通过阻断Atg8的脱脂，可以部分绕过对Hfl1的需要。结论我们的数据揭示了空泡膜蛋白的降解过程，该过程依赖于ESCRT下游的空泡相关Atg8，我们确定了Hfl1在Atg8膜靶向中的特定作用，Hfl1是一种从酵母到动植物的保守蛋白质。
BackgroundThe vacuole/lysosome is the final destination of autophagic pathways, but can also itself be degraded in whole or in part by selective macroautophagic or microautophagic processes. Diverse molecular mechanisms are involved in these processes, the characterization of which has lagged behind those of ATG-dependent macroautophagy and ESCRT-dependent endosomal multivesicular body pathways.ResultsHere we show that as yeast cells gradually exhaust available nutrients and approach stationary phase, multiple vacuolar integral membrane proteins with unrelated functions are degraded in the vacuolar lumen. This degradation depends on the ESCRT machinery, but does not strictly require ubiquitination of cargos or trafficking of cargos out of the vacuole. It is also temporally and mechanistically distinct from NPC-dependent microlipophagy. The turnover is facilitated by Atg8, an exception among autophagy proteins, and an Atg8-interacting vacuolar membrane protein, Hfl1. Lack of Atg8 or Hfl1 led to the accumulation of enlarged lumenal membrane structures in the vacuole. We further show that a key function of Hfl1 is the membrane recruitment of Atg8. In the presence of Hfl1, lipidation of Atg8 is not required for efficient cargo turnover. The need for Hfl1 can be partially bypassed by blocking Atg8 delipidation.ConclusionsOur data reveal a vacuolar membrane protein degradation process with a unique dependence on vacuole-associated Atg8 downstream of ESCRTs, and we identify a specific role of Hfl1, a protein conserved from yeast to plants and animals, in membrane targeting of Atg8.
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