‡Seahorse Bioscience, North Billerica, MA 01862, U.S.A.
§Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
Clin Sci (Lond). 2014 Sep;127(6):367-73. doi: 10.1042/CS20140101.
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.
生物能量学已成为我们理解病理机制、开发新治疗策略以及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的核心。一个关键概念是，线粒体可以作为“煤矿中的金丝雀”，通过作为患者人群中生物能量危机的早期预警来发挥作用。我们提出，需要新的临床测试来监测患者人群中生物能量的变化，以利用生物能量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。随着高通量测定细胞能量功能的新技术的发展，可以从人体血液中分离出少量细胞进行这些临床测试现在已经成为可能。我们已经表明，依次添加经过充分表征的氧化磷酸化抑制剂，可以测量从正常或病理样本中分离出的细胞的生物能量谱。从这些数据中，我们提出可以计算出单个值——生物能量健康指数（BHI）——来代表患者选定细胞类型的综合线粒体谱。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。我们提出，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。
