The Bioenergetic Health Index: a new concept in mitochondrial translational research.
The Bioenergetic Health Index: a new concept in mitochondrial translational research.
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DOI：
10.1042/cs20140101
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发表时间：
2014-09
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影响因子：
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通讯作者：
Darley-Usmar VM
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文献类型：
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作者：
Chacko BK;Kramer PA;Ravi S;Benavides GA;Mitchell T;Dranka BP;Ferrick D;Singal AK;Ballinger SW;Bailey SM;Hardy RW;Zhang J;Zhi D;Darley-Usmar VM
生物能量学已成为我们理解病理机制、开发新的治疗策略的核心，并作为神经退行性疾病、糖尿病、癌症和心血管疾病疾病进展的生物标志物。一个关键的概念是，通过对患者群体的生物能量危机进行早期预警，可以作为“煤矿中的金丝雀”。我们建议，需要新的临床试验来监测患者群体中生物能量学的变化，以利用生物能量学的早期和敏感能力来确定复杂和多因素疾病的严重程度和进展。随着近年来高通量测定法的发展，可以从人体血液中分离出少量细胞，用于测量细胞能量功能，这些临床测试现在是可行的。我们已经表明，顺序添加的特征良好的氧化磷酸化抑制剂允许生物能量的配置文件，以测量从正常或病理样品中分离的细胞。从这些数据中，我们提出了一个单一的值-生物能量健康指数（BHI）-可以计算代表选定的细胞类型的患者的复合线粒体档案。在本假说论文中，我们讨论了BHI如何作为生物能量健康的动态指标，以及如何在血小板和白细胞中进行测量。我们认为，最终，BHI有可能成为一种新的生物标志物，用于评估患者的健康状况，具有预后和诊断价值。
Bioenergetics has become central to our understanding of pathological mechanisms, the development of new therapeutic strategies and as a biomarker for disease progression in neurodegeneration, diabetes, cancer and cardiovascular disease. A key concept is that the mitochondrion can act as the ‘canary in the coal mine’ by serving as an early warning of bioenergetic crisis in patient populations. We propose that new clinical tests to monitor changes in bioenergetics in patient populations are needed to take advantage of the early and sensitive ability of bioenergetics to determine severity and progression in complex and multifactorial diseases. With the recent development of high-throughput assays to measure cellular energetic function in the small number of cells that can be isolated from human blood these clinical tests are now feasible. We have shown that the sequential addition of well-characterized inhibitors of oxidative phosphorylation allows a bioenergetic profile to be measured in cells isolated from normal or pathological samples. From these data we propose that a single value–the Bioenergetic Health Index (BHI)–can be calculated to represent the patient's composite mitochondrial profile for a selected cell type. In the present Hypothesis paper, we discuss how BHI could serve as a dynamic index of bioenergetic health and how it can be measured in platelets and leucocytes. We propose that, ultimately, BHI has the potential to be a new biomarker for assessing patient health with both prognostic and diagnostic value.