The Bioenergetic Health Index: a new concept in mitochondrial translational research

Abstract

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.

Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients

“…Recently, we have proposed that inflammatory cells, such as monocytes/macrophages, neutrophils or lymphocytes, can act as a biomarker of inflammation-associated mitochondrial dysfunction defined as changes in cellular bioenergetics [11][12][13]. Taken together, these findings suggested to us the hypothesis that the monocytes isolated from the PO-PCF, which is more pro-oxidant than the plasma, would exhibit increased mitochondrial dysfunction compared with cells isolated from the patients' blood.…”

“…We have recently demonstrated that the individual parameters from the mitochondrial stress test are interactive and that they can be integrated into a single value representing the profiles shown in Figures 1(A) and 1(B) known as the BHI [11]. As shown in Figure 2(A), BHI is significantly different (P = 0.030) between the healthy controls and the monocytes isolated from the blood from patients following surgery.…”

“…would be a more sensitive and accurate indicator of a patient's bioenergetic health [11]. To test this, we determined the BHI from the data shown in Figure 1(A) and found that, in contrast with the individual parameters from the mitochondrial stress test that BHI was decreased in the patients' monocytes relative to healthy controls ( Figure 2).…”

“…As shown in Figure 2(A), BHI is significantly different (P = 0.030) between the healthy controls and the monocytes isolated from the blood from patients following surgery. Although each bioenergetics parameter measured ( Figures 1A and 1B) was not significantly different between blood analysis of healthy donors and blood from cardiac surgery patients when compared independently, when integration of bioenergetic parameters using the BHI calculation is performed, a significant difference is now apparent (Figure 2A) [11]. This arises from the fact that the energetics parameters in the mitochondrial stress test are interactive and small changes in individual parameters cannot capture the overall change in the bioenergetic profile in response to stress.…”

“…We have shown that the parameters derived from the mitochondrial stress test respond in a co-ordinated fashion under conditions of oxidative stress [15,16]. We have used this approach with the values from the mitochondrial stress test to generate a single value known as the Bioenergetic Health Index (BHI) which provides an index of mitochondrial function in cells [11].…”