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FASEB J. 2013 Dec;27(12):4703-11. doi: 10.1096/fj.13-229476. Epub 2013 Aug 27.
Organ injury in sepsis is initially characterized by dysfunction without cell death and structural damage, and thus with the ability to recover organ function. Adaptive metabolic responses to sepsis can prevent bioenergetic failure and death. These studies were aimed at investigating the influence of sepsis on mitochondrial homeostasis, focusing on removal of dysfunctional mitochondria and restitution of a healthy mitochondrial population. These data demonstrate decreased hepatic oxidative phosphorylation by 31 ± 11% following murine cecal ligation and puncture (CLP) at 8 h and 34 ± 9% following LPS treatment in vitro at 12 h (P<0.05). In addition, there was a loss of mitochondrial membrane potential. Mitochondrial density and number initially decreased (relative area per micrograph of 64±10% at baseline vs. 39±13% at 8 h following LPS; P<0.05) and was associated with an increase in autophagy and mitophagy. CLP-induced markers of mitochondrial biogenesis and mitochondrial number and density recovered over time. Furthermore, these data suggest that mitochondrial biogenesis was dependent on an autophagy and mitochondrial DNA/Toll-like receptor 9 (TLR9) signaling pathway. These results suggest that hepatocyte survival and maintenance of function in sepsis is dependent on a mitochondrial homeostasis pathway marked by mitophagy and biogenesis.
脓毒症中的器官损伤最初表现为无细胞死亡和结构损伤的功能障碍，因此具有恢复器官功能的能力。脓毒症的适应性代谢反应可以防止生物能量衰竭和死亡。这些研究旨在调查脓毒症对线粒体动态平衡的影响，重点是清除功能失调的线粒体并恢复健康的线粒体群体。这些数据表明，在 8 小时的盲肠结扎和穿刺（CLP）后，小鼠的肝脏氧化磷酸化降低了 31 ± 11%，而在体外的 LPS 处理 12 小时后降低了 34 ± 9%（P<0.05）。此外，还存在线粒体膜电位的丧失。线粒体密度和数量最初减少（相对于基线的相对显微镜面积为 64±10%，而在 LPS 处理 8 小时后为 39±13%；P<0.05），并与自噬和线粒体自噬增加相关。CLP 诱导的线粒体生物发生和线粒体数量和密度的标志物随时间恢复。此外，这些数据表明，线粒体生物发生依赖于自噬和线粒体 DNA/Toll 样受体 9（TLR9）信号通路。这些结果表明，脓毒症中肝细胞的存活和功能维持依赖于以线粒体自噬和生物发生为标志的线粒体动态平衡途径。
