Victor Darley-Usmar measures how well cells make energy under stress – and says his system could be as useful to doctors as a blood pressure meter
You stress the importance of bioenergetics. What is it?
It's a broad term in biology that refers to how energy is produced and used. We focus on the cellular level, primarily with mitochondria, which produce the energy used by the cell.
How can it measure how healthy we are?
We are developing a measure called the Bioenergetics Health Index (BHI) that we believe can be used to predict the response to stressors such as diabetes or infection. The plan is to have an index, similar to blood pressure, so we know that if the BHI is below a certain range point, the body is more susceptible to disease.
To calculate BHI, we measure oxygen used by a cell at rest and then under a defined metabolic stress – and then look at the difference between the two. We can use oxygen consumption as a marker of how much energy mitochondria are able to generate. The cell needs a certain level of energy to carry out basic functions and even more to deal with stressors like disease.
So BHI could serve as a warning system?
There are different patterns of BHI, perhaps a different one for each disease. For example, excessive fat causes inflammation involving white blood cells. Part of the BHI calculation is based on circulating-white-blood-cell count, and we believe this component could be the canary in the coal mine for susceptibility to diseases such as diabetes and cardiovascular disease.
We have promising initial data from three ongoing pilot studies in patients with kidney disease, alcohol-related disease and HIV that shows differences in BHI between the patient populations. Of course this is just a snapshot in time of different people. But hopefully that will give us a platform to get to much more comprehensive long-term studies to better understand cause and effect.
Could BHI change our understanding of how diseases progress?
Yes. Another example is obesity. Some obese people remain healthy while others quickly develop metabolic diseases such as increased blood pressure and decreased kidney function. How sensitive you are to these diseases and how fast you progress may depend upon how well your body can make energy to combat that stress. That's what BHI adds to the picture.
Are changes in bioenergetics the cause of disease or the result?
It is likely an interplay of both, depending upon the disease. But we don't know that yet for sure, which is why we need to do long-term studies.
How will BHI change medical care?
Two people can have the same symptoms for a disease but their mechanisms can be quite different. Your blood pressure could be high for one reason and mine high for another. We hope that BHI will provide another tool for doctors to drill down to the underlying molecular mechanisms of the individual patient's disease, and then choose the appropriate intervention.
This article appeared in print under the headline "Cells speak volumes"
Profile
Victor Darley-Usmar is a biochemist at the University of Alabama at Birmingham who studies mitochondria, the powerhouse of the cell. His current work explores the relationship between cell energy levels and health
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