Both Sides of the Equation

By Shona Mookerjee, PhD
Assistant Professor & Curriculum Coordinator for the College of Pharmacy Department of Biological and Pharmaceutical Sciences

Dr. Shona Mookerjee

Dr. Shona Mookerjee's work with colleagues Akos Gerencser, David Nicholls, and Martin Brand was recently selected as the representative Bioenergetics article for The Journal of Biological Chemistry's "This year in JBC: 2017". Dr. Mookerjee's, Quantifying Intracellular Rates of Glycolytic and Oxidative ATP Production and Consumption Using Extracellular Flux Measurementswas chosen from the journal's nearly 2,000 papers published in 2017. Below she explains the role that ATP plays in the body and why it is important to view both sides of the ATP-producing machinery at the same time.

It’s a small molecule with a big impact. ATP (Adenosine Tri-Phosphate) is the metabolic “gasoline” that fuels most biological activities— including your heart’s pumping, your body’s movement, and the brainpower that you are using right now to read this sentence. Altogether, you burn through your own body weight in ATP each day—and you make it just as quickly. Knowing the rate at which your cells make ATP, and how that is balanced with the rate of its use, can change the way we think about how cells “budget” their energy to survive and thrive and whether energy imbalances underlie conditions including cancer, aging, and many others.

For decades, researchers have had half the story. There are two main ATP production pathways—one pathway consumes oxygen, and is the reason we need to breathe. The other pathway bypasses oxygen and instead makes lactic acid, something that anyone who has experienced muscle fatigue can appreciate. These two pathways were difficult to examine together because the two signals (oxygen consumption and lactate production) have needed separate instruments to detect them. And knowing only one rate yields at best an incomplete answer.

As an example, imagine that your friend texts you “Enjoying spicy street food at 19 degrees N”. That’s great for them, but since you only know their latitude, you don’t know whether they are in Mexico City, or in Mumbai! You would also need their longitude to better understand their location.

It’s the same for cellular ATP production rate. With a new instrument that uses fluorescent signals to measure each signal simultaneously in living cells, in combination with “old-fashioned” chemistry principles, we have developed a framework for calculating how much ATP each pathway is making in the same cells at the same time—equivalent to knowing your friend’s latitude and longitude at the same time. We are using this new approach to investigate how changes to ATP supply and demand might influence conditions including cancer, aging, and different disease states. Further, this approach can be used to test the metabolic effects of drugs used to treat these conditions, and help guide the development of new ones.