Department of Biological Sciences, Ferris State University, Big Rapids, MI 49307, USA.
Department of Genetics, Cell Biology, and Developmental Biology, University of Minnesota, Minneapolis, MN 55455, USA.
Genetics. 2023 Oct 4;225(2). doi: 10.1093/genetics/iyad154.
Autophagy, an autophagosome and lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes Atg1 or Atg18 in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies but the lifespan reduction phenotype has become apparent when Atg1 RNAi or Atg18 RNAi is expressed ubiquitously in adult flies or after autophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and midgut stem cells. Overexpression of wild-type Atg1 in adult fly muscle or adipocytes reduces the lifespan and causes accumulation of high levels of ubiquitinated protein aggregates in muscles. Our research data have highlighted the important functions of the key autophagy genes in adult fly adipocytes, enteroblasts, and midgut stem cells and their undetermined roles in adult fly muscle and glia for lifespan regulation.
自噬是一种基于自噬体和溶酶体的真核细胞降解系统，先前已被发现在不同的动物模型中参与寿命调节。在本报告中，我们表明，靶向关键自噬基因 Atg1 或 Atg18 转录本的 RNAi 转基因在成年果蝇肌肉或神经胶质中的表达不会影响这些组织中自噬体的总体水平，也不会改变测试果蝇的寿命，但当 Atg1 RNAi 或 Atg18 RNAi 在成年果蝇中普遍表达时，或者当通过敲低 Atg1 或 Atg18 在成年果蝇脂肪细胞中消除自噬时，寿命缩短表型变得明显。当 Atg1 或 Atg18 在成年果蝇肠细胞和中肠干细胞中被敲低时，也观察到寿命缩短。野生型 Atg1 在成年果蝇肌肉或脂肪细胞中的过表达会缩短寿命，并导致肌肉中高水平的泛素化蛋白聚集体积累。我们的研究数据突出了关键自噬基因在成年果蝇脂肪细胞、肠细胞和中肠干细胞中的重要功能，以及它们在成年果蝇肌肉和神经胶质中对寿命调节的未确定作用。
