Growth cones, found at the tips of growing axons in developing neurons, use dynamic extensions of the plasma membrane to mediate axon growth and guidance, requiring significant ATP-dependent remodelling of the actin cytoskeleton. This had been previously proposed to consume up to 50% of the cellular ATP, suggesting that actin dynamics alone represent an enormous bioenergetic drain in neurons. However, based on more recent work, it appears that the homeostatic ATP/ADP ratio in neurons is tightly controlled, even when metabolic demand is acutely increased. Here (Holland and Gallo, 2023), Sabrina Holland and Gianluca Gallo revisit the impact actin dynamics have on neuronal energy homeostasis using modern, genetically encoded reporters in cultured chicken sensory neurons. In contrast to previous findings, they report that inhibiting growth cone remodelling by disrupting actin filament growth and turnover does not significantly increase levels of available ATP either locally or in neuronal cell bodies. Similarly, the local ATP/ADP ratio in growth cones remains stable when morphological remodelling is induced with nerve growth factor (NGF), which dramatically increases actin dynamics. These data thus provide a timely update to our understanding of how neurons maintain energy homeostasis despite the many specialised energy-demanding cellular processes they rely on to function, and also demonstrate the importance of reexamining prevailing hypotheses using more sensitive and accurate techniques.
