Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Cell Death Differ. 2022 Nov;29(11):2275-2287. doi: 10.1038/s41418-022-01014-y. Epub 2022 May 6.
Autophagy targets cytoplasmic materials for degradation, and influences cell health. Alterations in Atg6/Beclin-1, a key regulator of autophagy, are associated with multiple diseases. While the role of Atg6 in autophagy regulation is heavily studied, the role of Atg6 in organism health and disease progression remains poorly understood. Here, we discover that loss of Atg6 in Drosophila results in various alterations to stress, metabolic and immune signaling pathways. We find that the increased levels of circulating blood cells and tumor-like masses in atg6 mutants vary depending on tissue-specific function of Atg6, with contributions from intestine and hematopoietic cells. These phenotypes are suppressed by decreased function of macrophage and inflammatory response receptors crq and drpr. Thus, these findings provide a basis for understanding how Atg6 systemically regulates cell health within multiple organs, and highlight the importance of Atg6 in inflammation to organismal health.
自噬靶向细胞质物质进行降解，并影响细胞健康。自噬关键调节因子 Atg6/Beclin-1 的改变与多种疾病有关。虽然 Atg6 在自噬调节中的作用已被广泛研究，但 Atg6 在机体健康和疾病进展中的作用仍知之甚少。在这里，我们发现果蝇中 Atg6 的缺失会导致应激、代谢和免疫信号通路的各种改变。我们发现，atg6 突变体中循环血细胞和肿瘤样肿块的增加水平取决于 Atg6 的组织特异性功能，肠和造血细胞都有贡献。这些表型可被巨噬细胞和炎症反应受体 crq 和 drpr 功能降低所抑制。因此，这些发现为理解 Atg6 如何在多个器官中系统性地调节细胞健康提供了基础，并强调了 Atg6 在炎症对机体健康中的重要性。
