Regulation of mitochondrial nutrient and energy metabolism by BCL-2 family proteins

• Select BCL-2 family proteins control mitochondrial substrate and energy metabolism.
• Metabolic functions of BCL-2 proteins can be independent of cell death regulation.
• Metabolic effects of BCL-2 proteins can alter cellular and systemic physiology.

Cells have evolved a highly integrated network of mechanisms to coordinate cellular survival/death, proliferation, differentiation, and repair with metabolic states. It is therefore not surprising that proteins with canonical roles in cell death/survival also modulate nutrient and energy metabolism and vice versa. The finding that many BCL-2 (B cell lymphoma 2) proteins reside at mitochondria or can translocate to this organelle has long motivated investigation into their involvement in normal mitochondrial physiology and metabolism. These endeavors have led to the discovery of homeostatic roles for BCL-2 proteins beyond apoptosis. We predominantly focus on recent findings that link select BCL-2 proteins to carbon substrate utilization at the level of mitochondrial fuel choice, electron transport, and metabolite import independent of their cell death regulatory function.