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

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 - Clin. Sci. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ‡Seahorse Bioscience, North Billerica, MA 01862, U.S.A.

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.

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Related in: MedlinePlus

Cellular mitochondrial profile in human monocytesThis assay defines cellular mitochondrial function using the well-definedinhibitors, oligomycin (Oligo), FCCP and antimycin A (AntiA) [12]. The interpretation of the differentparameters defined by the assay is described in the accompanying text. Data istypically normalized to total protein or cell number in each well. Values aremeans±S.E.M., n=3–5.
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Figure 2: Cellular mitochondrial profile in human monocytesThis assay defines cellular mitochondrial function using the well-definedinhibitors, oligomycin (Oligo), FCCP and antimycin A (AntiA) [12]. The interpretation of the differentparameters defined by the assay is described in the accompanying text. Data istypically normalized to total protein or cell number in each well. Values aremeans±S.E.M., n=3–5.

Mentions: Parameters from the cellular mitochondrial function assay (Figure 2) give insights into different aspects of mitochondrial function andbelow we discuss how these can be used to calculate the BHI. An important aspect ofthese mitochondrial parameters that can be measured from this assay is that they arepotentially interactive and, taken together, can serve as a sensitive indicator of theresponse of cells to oxidative stress and the changing metabolic programmes associatedwith their role in inflammation.


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

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 - Clin. Sci. (2014)

Cellular mitochondrial profile in human monocytesThis assay defines cellular mitochondrial function using the well-definedinhibitors, oligomycin (Oligo), FCCP and antimycin A (AntiA) [12]. The interpretation of the differentparameters defined by the assay is described in the accompanying text. Data istypically normalized to total protein or cell number in each well. Values aremeans±S.E.M., n=3–5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202728&req=5

Figure 2: Cellular mitochondrial profile in human monocytesThis assay defines cellular mitochondrial function using the well-definedinhibitors, oligomycin (Oligo), FCCP and antimycin A (AntiA) [12]. The interpretation of the differentparameters defined by the assay is described in the accompanying text. Data istypically normalized to total protein or cell number in each well. Values aremeans±S.E.M., n=3–5.
Mentions: Parameters from the cellular mitochondrial function assay (Figure 2) give insights into different aspects of mitochondrial function andbelow we discuss how these can be used to calculate the BHI. An important aspect ofthese mitochondrial parameters that can be measured from this assay is that they arepotentially interactive and, taken together, can serve as a sensitive indicator of theresponse of cells to oxidative stress and the changing metabolic programmes associatedwith their role in inflammation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ‡Seahorse Bioscience, North Billerica, MA 01862, U.S.A.

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.

Show MeSH
Related in: MedlinePlus