Transitional correlation between inner-membrane potential and ATP levels of neuronal mitochondria

The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMPmito), and little is known about the dynamics of native mitochondrial ATP (ATP(mito)). This study conducted simultaneous imaging of IMPmito and ATP(mito) in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity. We found that mitochondrial size, transport velocity and transport direction are not dependent on ATP(mito) or IMPmito. However, changes in ATP(mito) and IMPmito during mitochondrial fission/fusion were found; IMPmito depolarized via mitochondrial fission and hyperpolarized via fusion, and ATP(mito) levels increased after fusion. Because the density of mitochondria is higher in growth cones (GCs) than in axonal processes, integrated ATP(mito) signals (density x ATP(mito)) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation between IMPmito in GCs and axonal elongation. A detailed timecourse analysis performed to clarify the reason for these discrepancies showed that IMPmito and ATP(mito) levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.