SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential

Abstract

AbstractCytochrome c is an essential component of the electron transport chain (ETC), which regulates respiratory chain activity, oxygen consumption, and ATP synthesis. But the impact of conformational changes in cytochrome c on its function is not understood for lack of access to these changes in intact mitochondria. Here we describe a label-free tool that identifies conformational changes in cytochrome c heme and elucidates their function. We verify that molecule bond vibrations assessed by surface-enhanced Raman spectroscopy (SERS) is a reliable indicator of the planar heme configuration during activation of ETC and decrease in inner mitochondrial membrane potential. The planar conformation of cytochrome c heme enables its optimal orientation towards the heme of cytochrome c1 in complex III. This ensures a faster electron transfer, which is important during ETC speed-ups and acceleration of ATP synthesis. The ability of our tool to track mitochondrial function opens wide perspectives on cell bioenergetics.