A physiological Na+ signal activates mitochondrial PINK1 to couple synaptic depression to caspase-3-dependent spine pruning

Na+ influx through NMDA receptors during chemically induced LTD depolarizes dendritic mitochondria, triggering translation-dependent PINK1 stabilization and activation that drives asynchronous mitochondrial fission.

• Why it matters: Synapse elimination during LTD involves caspase-3 activation linked to mitochondria-derived apoptotic signals, but the upstream Na+-to-mitochondria coupling mechanism was unknown.
• What they did: In cultured neurons, chemically induced LTD was used to test whether NMDA-receptor Na+ influx and PINK1 control mitochondrial fission, caspase-3 activation, and spine morphology.
• The result: Na+ influx and PINK1 are required for cLTD-induced fission; blocking either prevents caspase-3 activation and spine shrinking, linking Na+-PINK1 signaling to caspase-3-dependent synapse elimination during LTD.