Ambre Bertholet, Ph.D.

Research

The Bertholet lab will study how mitochondria, which produce cellular energy in the form of ATP, can instead be steered toward generating heat. Mitochondrial heat production is crucial for thermoregulation and for burning excess calories. As a postdoctoral fellow, I discovered that a transport protein that allows mitochondria to export ATP also permits protons to enter. This leakage dissipates the stockpile of protons that is built up by the oxidation of food and that serves as a source of “stored energy” that mitochondria tap to power ATP synthesis. If protons are coming in faster than they are building up to produce heat, the mitochondria must burn food to maintain the necessary level of ATP for the cell's needs. Now, using both traditional and modern techniques in cellular and molecular genetics combined with a method I developed for monitoring mitochondrial activity, I will identify the structural features within this transport protein that cause it to switch from shepherding ATP to leaking protons, isolate any protein partners that promote this leakage, and develop novel chemical activators that can stimulate this heat-producing activity. My work could produce novel therapies for combatting conditions associated with mitochondrial dysfunction, including obesity, diabetes, and disorders associated with aging.