Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Development, Genetics and Molecular Physiology, LIMES (Life and Medical Sciences), University of Bonn, D-53115 Bonn, Germany.
Mol Biol Cell. 2018 Nov 1;29(22):2766-2783. doi: 10.1091/mbc.E18-07-0434. Epub 2018 Sep 6.
The gut has a central role in digestion and nutrient absorption, but it also serves in defending against pathogens, engages in mutually beneficial interactions with commensals, and is a major source of endocrine signals. Gut homeostasis is necessary for organismal health and changes to the gut are associated with conditions like obesity and diabetes and inflammatory illnesses like Crohn's disease. We report that peroxisomes, organelles involved in lipid metabolism and redox balance, are required to maintain gut epithelium homeostasis and renewal in Drosophila and for survival and development of the organism. Dysfunctional peroxisomes in gut epithelial cells activate Tor kinase-dependent autophagy that increases cell death and epithelial instability, which ultimately alter the composition of the intestinal microbiota, compromise immune pathways in the gut in response to infection, and affect organismal survival. Peroxisomes in the gut effectively function as hubs that coordinate responses from stress, metabolic, and immune signaling pathways to maintain enteric health and the functionality of the gut-microbe interface.
肠道在消化和营养吸收中起着核心作用，但它也能抵御病原体，与共生菌进行互利的相互作用，并且是内分泌信号的主要来源。肠道内环境的稳定对于机体的健康是必要的，而肠道的变化与肥胖症、糖尿病和炎症性疾病（如克罗恩病）等疾病有关。我们报告称，参与脂质代谢和氧化还原平衡的细胞器——过氧化物酶体，对于维持果蝇肠道上皮细胞的内环境稳定和更新，以及机体的生存和发育是必需的。肠道上皮细胞中功能失调的过氧化物酶体激活 Tor 激酶依赖性自噬，增加细胞死亡和上皮细胞不稳定，最终改变肠道微生物群的组成，损害对感染的肠道免疫途径，并影响机体的生存。肠道中的过氧化物酶体有效地作为枢纽，协调来自应激、代谢和免疫信号通路的反应，以维持肠道健康和肠道-微生物界面的功能。
