Eleftheriadis Theodoros, Pissas Georgios, Liakopoulos Vassilios, Stefanidis Ioannis
Department of Nephrology, Medical School, University of Thessaly , Larissa , Greece.
Front Immunol. 2016 Jul 20;7:279. doi: 10.3389/fimmu.2016.00279. eCollection 2016.
Mitochondria are evolutionary endosymbionts derived from bacteria. Thus, they bear molecules, such as mitochondrial DNA (mtDNA) that contains CpG DNA repeats and N-formyl peptides (FPs), found in bacteria. Upon cell necrosis or apoptosis, these molecules are released into the interstitial space and the circulation and recognized by the immune cells through the same receptors that recognize pathogen-associated molecular patterns, leading to inflammation. Other mitochondrial molecules are not of bacterial origin, but they may serve as danger-associated molecular patterns (DAMPs) when due to cell injury are translocated into inappropriate compartments. There they are recognized by pattern recognition receptors of the immune cells. Cytochrome c is such a molecule. In this review, experimental and clinical data are presented that confirms cytochrome c release into the extracellular space in pathological conditions characterized by cell death. This indicates that serum cytochrome c, which can be easily measured, may be a clinically useful marker for diagnosing and assessing the severity of such pathological entities. Reasonably, detection of high cytochrome c level into the circulation means release of various other molecules that serves as DAMPs when found extracellularly, the mtDNA and FPs included. Finally, because the release of this universally found compound into the extracellular space makes cytochrome c an ideal molecule to play the role of a DAMP per se, the available experimental and clinical data that support such a role are provided.
线粒体是源自细菌的进化性内共生体。因此，它们携带一些分子，如含有CpG DNA重复序列和N-甲酰肽（FPs）的线粒体DNA（mtDNA），这些在细菌中也能找到。在细胞坏死或凋亡时，这些分子会释放到组织间隙和循环系统中，并被免疫细胞通过识别病原体相关分子模式的相同受体识别，从而引发炎症。其他线粒体分子并非源自细菌，但当由于细胞损伤而转移到不适当的区室时，它们可能作为危险相关分子模式（DAMPs）发挥作用。在那里，它们被免疫细胞的模式识别受体识别。细胞色素c就是这样一种分子。在这篇综述中，展示了实验和临床数据，证实了在以细胞死亡为特征的病理条件下细胞色素c释放到细胞外空间。这表明血清细胞色素c（可轻松检测）可能是诊断和评估此类病理实体严重程度的临床有用标志物。合理地说，在循环系统中检测到高细胞色素c水平意味着释放了各种其他分子，当这些分子在细胞外被发现时可作为DAMPs，包括mtDNA和FPs。最后，由于这种普遍存在的化合物释放到细胞外空间使细胞色素c本身成为发挥DAMP作用的理想分子，因此提供了支持这种作用的现有实验和临床数据。
