Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes.
Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes.
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果蝇 Caliban 通过调节肠细胞中的线粒体动力学和氧化还原状态来保持肠道稳态和寿命
DOI：
10.1371/journal.pgen.1009140
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发表时间：
2020-10
期刊：
影响因子：
4.5
通讯作者：
Bi X
中科院分区：
文献类型：
--
作者：
Dai Z;Li D;Du X;Ge Y;Hursh DA;Bi X
干细胞活性的精确调节对于组织稳态至关重要。在果蝇中，肠干细胞（ISCs）维持中肠上皮细胞并对氧化挑战做出反应。然而，肠道内稳态和氧化还原信号之间的联系仍然不清楚。在这里，我们发现，Caliban（Clbn）的功能作为肠上皮细胞（EC）的线粒体动力学的调节剂，是肠道稳态所需的。clbn基因敲除的果蝇寿命缩短，失去肠道内稳态。Clbn在EC中高度表达并定位于线粒体的外膜。在机械上，Clbn介导EC中的线粒体动力学，并且clbn的去除导致线粒体片段化、活性氧簇的积累、EC损伤、JNK和JAK-STAT信号通路的激活。此外，通过全基因组转录谱分析，野生型和clbn突变的果蝇之间存在多个与果蝇相关的基因的差异表达。此外，clbn的缺失促进肠祖细胞中激活的Ras产生的肠中肿瘤生长。我们的研究结果揭示了EC特异性功能的Clbn在调节线粒体动力学，线粒体氧化还原调节，组织稳态和寿命之间的功能联系提供了新的见解。
Precise regulation of stem cell activity is crucial for tissue homeostasis. In Drosophila, intestinal stem cells (ISCs) maintain the midgut epithelium and respond to oxidative challenges. However, the connection between intestinal homeostasis and redox signaling remains obscure. Here we find that Caliban (Clbn) functions as a regulator of mitochondrial dynamics in enterocytes (ECs) and is required for intestinal homeostasis. The clbn knock-out flies have a shortened lifespan and lose the intestinal homeostasis. Clbn is highly expressed and localizes to the outer membrane of mitochondria in ECs. Mechanically, Clbn mediates mitochondrial dynamics in ECs and removal of clbn leads to mitochondrial fragmentation, accumulation of reactive oxygen species, ECs damage, activation of JNK and JAK-STAT signaling pathways. Moreover, multiple mitochondria-related genes are differentially expressed between wild-type and clbn mutated flies by a whole-genome transcriptional profiling. Furthermore, loss of clbn promotes tumor growth in gut generated by activated Ras in intestinal progenitor cells. Our findings reveal an EC-specific function of Clbn in regulating mitochondrial dynamics, and provide new insight into the functional link among mitochondrial redox modulation, tissue homeostasis and longevity.
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