School of Life Sciences, University of Warwick, CV4 7AL Coventry, UK.
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
Cell Rep. 2020 May 26;31(8):107695. doi: 10.1016/j.celrep.2020.107695.
Autophagy is the degradation of cytoplasmic material through the lysosomal pathway. One of the most studied autophagy-related proteins is LC3. Despite growing evidence that LC3 is enriched in the nucleus, its nuclear role is poorly understood. Here, we show that Drosophila Atg8a protein, homologous to mammalian LC3, interacts with the transcription factor Sequoia in a LIR motif-dependent manner. We show that Sequoia depletion induces autophagy in nutrient-rich conditions through the enhanced expression of autophagy genes. We show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex, and that it is acetylated in nutrient-rich conditions. We also show that Atg8a interacts with the deacetylase Sir2, which deacetylates Atg8a during starvation to activate autophagy. Our results suggest a mechanism of regulation of the expression of autophagy genes by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL-1, and Sir2.
自噬是通过溶酶体途径降解细胞质物质的过程。研究最多的自噬相关蛋白之一是 LC3。尽管越来越多的证据表明 LC3 在核内富集，但它的核内作用仍知之甚少。在这里，我们表明果蝇 Atg8a 蛋白与哺乳动物 LC3 同源，以 LIR 基序依赖的方式与转录因子 Sequoia 相互作用。我们表明，在营养丰富的条件下，通过增强自噬基因的表达，Sequoia 的耗竭会诱导自噬。我们表明 Atg8a 与 YL-1 相互作用，YL-1 是核乙酰转移酶复合物的一个组成部分，并且在营养丰富的条件下被乙酰化。我们还表明，Atg8a 与去乙酰化酶 Sir2 相互作用，在饥饿时 Sir2 去乙酰化 Atg8a 以激活自噬。我们的结果表明了一种通过 Atg8a 调节自噬基因表达的机制，该机制与其乙酰化状态及其与 Sequoia、YL-1 和 Sir2 的相互作用有关。
