The Role of Mitochondrially Derived ATP in Synaptic Vesicle Recycling

摘要: Synaptic mitochondria are thought to be critical in supporting neuronal energy requirements at the synapse, and bioenergetic failure synapse may impair neural transmission contribute neurodegeneration. However, little is known about of synaptic vesicle release or whether these go unmet disease, primarily due a lack appropriate tools sensitive assays. To determine dependence cycling on mitochondrially derived ATP levels, we developed two complementary assays individual, living hippocampal boutons. The first functional assay for that uses extent as surrogate level. second FRET sensors directly measure synapse. Using assays, show endocytosis has high reacidification exocytosis require comparatively energy. We then meet needs, rapidly dispersed axons, thereby maintaining near normal levels even boutons lacking mitochondria. As result, capacity similar without those with Finally, loss key respiratory subunit implicated Leigh disease markedly decreases thus inhibiting cycling. This proves mitochondria-based can occur detected individual neurons have genetic mitochondrial defect.