Wake Forest University School of Medicine has received a $1.9 million grant from the National Institute of General Medical Sciences, part of the National Institutes of Health, to support research that challenges conventional scientific thinking about how cells convert energy.
The five-year study led by Dhanendra Tomar, Ph.D., assistant professor of cardiovascular medicine, focuses on a foundational discovery about proteins that could lead to new preventative treatments for a variety of diseases.
The research looks at mitochondrial calcium uptake (MICU) proteins. Scientists have long believed these proteins just control calcium flow into mitochondria, which are like power plants inside cells. Tomar’s team found these proteins actually have a second job that changes what we know about how cells work.
“This discovery overturns years of scientific assumptions,” Tomar said. “For more than 10 years of mitochondrial calcium research, these proteins were viewed as having only one function. When we found they had additional roles, it opened an entirely new direction for research that could impact every area of human health.”
The discovery happened by accident when researchers removed calcium channels from mitochondria completely, expecting MICU proteins to disappear as well.
“These proteins were still standing there like soldiers ready for duty, even when there was no gate to guard,” Tomar said. “That made us realize they must be doing something else.”
Upon further tests, Tomar and his team learned the MICU proteins also organized the inside of mitochondria by arranging tiny folds that optimize energy conversion in cells.
To help explain this complex process, Tomar uses a simple comparison: imagine each cell as a factory that converts energy, with mitochondria as the main floor where the work happens. Calcium is the raw material the factory needs to keep machines running. MICU proteins act like factory foremen with two key jobs — controlling the supply gates to decide how much calcium comes in and organizing the factory floor to make energy conversion more efficient.
Understanding this dual role is crucial because when mitochondria break down, cells don’t have enough energy and organs start failing.
“All human diseases have mitochondrial dysfunction at their core,” Tomar said. “In heart disease, heart cells don’t function properly. In brain diseases like Alzheimer’s and Parkinson’s, brain cell mitochondria also fail. Even diabetes occurs because mitochondria can’t properly utilize the food we eat to generate energy.”
When calcium gets out of balance, mitochondria overload and start leaking. Since mitochondria originated from bacteria billions of years ago, cells treat leaked material like an infection and destroy themselves. This process has been observed in major conditions including heart failure, Alzheimer’s, Parkinson’s, diabetes and COVID-19.
Given how widespread these conditions are, this discovery offers hope for new approaches to disease. Instead of focusing on treatment after disease develops, this research could lead to therapies that protect cells from damage, potentially slowing or even preventing diseases affecting millions.
The grant will fund a study that specifically tests whether MICU proteins work the same way in different types of cells and whether each protein in the family has its own specific job. Tomar thinks new treatments based on this work could be ready in five to 10 years.
Wake Forest University School of Medicine is one of only a handful of institutions worldwide exploring this emerging area of mitochondrial biology. Collaborating universities include Vanderbilt University School of Medicine, UT Southwestern Medical Center, Temple University and UT Health San Antonio.
Media Contact:
Myra Wright, myra.wright@advocatehealth.org