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 (IMP_mito), and little is known about the dynamics of native mitochondrial ATP (ATP_mito). This study conducted simultaneous imaging of IMP_mito 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 IMP_mito. However, changes in ATP_mito and IMP_mito during mitochondrial fission/fusion were found; IMP_mito 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 × ATP_mito) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMP_mito was relatively hyperpolarized in GCs, there was no correlation between IMP_mito in GCs and axonal elongation. A detailed time-course analysis performed to clarify the reason for these discrepancies showed that IMP_mito and ATP_mito levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.