ATP has a limited diffusion capacity in axons, so locally anchored presynaptic mitochondria may be used to support high metabolic demand. Only 33% of presynaptic active zones in hippocampi retain mitochondria. Sustained synaptic activity is mainly restricted to these mitochondria-containing synapses during long-term potentiation. Li et al. investigated whether increased energy consumption during intensive synaptic activity contributes to presynaptic energy stress and how mitochondria are recruited to synapses. Syntaphilin (SNPH) anchors axonal mitochondria, and deleting snph enhances axonal mitochondrial motility in vitro and in vivo. Synaptic activity induces presynaptic energy stress, which activates the AMPK-PAK signaling cascade, triggering presynaptic mitochondrial recruitment and SNPH-mediated anchoring. Cross-talk between energy sensing and mitochondrial anchoring enables neurons to capture presynaptic mitochondria in response to local energy stress during intensive synaptic activity.
Nat. Metab. 2, 1077 (2020).
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