PDF(Pubmed)
Abstract：
Mitochondrial dysfunction critically contributes to many major human diseases. The impact of specific gut microbial metabolites on mitochondrial functions of animals and the underlying mechanisms remain to be uncovered. Here, we report a profound role of bacterial peptidoglycan muropeptides in promoting mitochondrial functions in multiple mammalian models. Muropeptide addition to human intestinal epithelial cells (IECs) leads to increased oxidative respiration and ATP production and decreased oxidative stress. Strikingly, muropeptide treatment recovers mitochondrial structure and functions and inhibits several pathological phenotypes of fibroblast cells derived from patients with mitochondrial disease. In mice, muropeptides accumulate in mitochondria of IECs and promote small intestinal homeostasis and nutrient absorption by modulating energy metabolism. Muropeptides directly bind to ATP synthase, stabilize the complex, and promote its enzymatic activity in vitro, supporting the hypothesis that muropeptides promote mitochondria homeostasis at least in part by acting as ATP synthase agonists. This study reveals a potential treatment for human mitochondrial diseases.
摘要：
线粒体功能障碍是许多重大人类疾病的关键原因。特定肠道微生物代谢产物对动物线粒体功能的影响及其潜在机制仍有待揭示。这里,我们报道了细菌肽聚糖肌醇肽在多种哺乳动物模型中促进线粒体功能的重要作用.人肠上皮细胞（IECs）中添加的Muropeptip导致氧化呼吸和ATP产生增加以及氧化应激降低。引人注目的是，muropeptip治疗可恢复线粒体结构和功能，并抑制线粒体疾病患者成纤维细胞的几种病理表型。在老鼠身上,肌肽在IECs的线粒体中积累，并通过调节能量代谢促进小肠稳态和营养吸收。肌肽直接结合ATP合成酶，稳定复合物，并促进其体外酶活性，支持以下假设：muropeptides至少部分通过充当ATP合酶激动剂来促进线粒体稳态。这项研究揭示了人类线粒体疾病的潜在治疗方法。
