Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
Mol Cell. 2016 Oct 20;64(2):221-235. doi: 10.1016/j.molcel.2016.09.008.
Autophagy is a potent cellular degradation pathway, and its activation needs to be tightly controlled. Cargo receptors mediate selectivity during autophagy by bringing cargo to the scaffold protein Atg11 and, in turn, to the autophagic machinery, including the central autophagy kinase Atg1. Here we show how selective autophagy is tightly regulated in space and time to prevent aberrant Atg1 kinase activation and autophagy induction. We established an induced bypass approach (iPass) that combines genetic deletion with chemically induced dimerization to evaluate the roles of Atg13 and cargo receptors in Atg1 kinase activation and selective autophagy progression. We show that Atg1 activation does not require cargo receptors, cargo-bound Atg11, or Atg13 per se. Rather, these proteins function in two independent pathways that converge to activate Atg1 at the vacuole. This pathway architecture underlies the spatiotemporal control of Atg1 kinase activity, thereby preventing inappropriate autophagosome formation.
自噬是一种强大的细胞降解途径，其激活需要严格控制。货物受体通过将货物带到支架蛋白 Atg11 上，并进而传递到自噬机制，包括中央自噬激酶 Atg1，从而在自噬过程中发挥选择性。在这里，我们展示了如何在空间和时间上严格调节选择性自噬，以防止异常的 Atg1 激酶激活和自噬诱导。我们建立了一种诱导旁路方法（iPass），该方法将遗传缺失与化学诱导二聚化相结合，以评估 Atg13 和货物受体在 Atg1 激酶激活和选择性自噬进展中的作用。我们表明，Atg1 的激活不需要货物受体、货物结合的 Atg11 或 Atg13 本身。相反，这些蛋白在两条独立的途径中发挥作用，这些途径会聚以在液泡处激活 Atg1。这种途径结构是 Atg1 激酶活性的时空控制的基础，从而防止了不适当的自噬体形成。
