Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage.
Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage.
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DOI：
10.3389/fimmu.2016.00279
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发表时间：
2016
影响因子：
7.3
通讯作者：
Stefanidis I
中科院分区：
文献类型：
--
作者：
Eleftheriadis T;Pissas G;Liakopoulos V;Stefanidis I
线粒体是一种由细菌进化而来的内共生体。因此，它们携带分子，例如在细菌中发现的含有CpG DNA重复序列和N-甲酰肽（FP）的线粒体DNA（mtDNA）。在细胞坏死或凋亡时，这些分子被释放到间质空间和循环中，并通过识别病原体相关分子模式的相同受体被免疫细胞识别，导致炎症。其他线粒体分子不是细菌来源的，但当由于细胞损伤而易位到不适当的隔室中时，它们可以作为线粒体相关分子模式（DAMP）。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，实验和临床数据证实细胞色素c释放到细胞外空间的病理条件下，其特征在于细胞死亡。这表明，血清细胞色素c，可以很容易地测量，可能是一个临床上有用的标记物，用于诊断和评估这些病理实体的严重程度。合理地，检测到高水平的细胞色素c进入循环意味着释放各种其他分子，当在细胞外发现时，这些分子作为DAMP，包括mtDNA和FP。最后，由于这种普遍发现的化合物释放到细胞外空间使细胞色素c成为发挥DAMP本身作用的理想分子，因此提供了支持这种作用的可用实验和临床数据。
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.