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<p>MINFLUX is a cutting-edge single-molecule localization microscopy technology that surpasses the conventional diffraction limit, enabling nanostructure visualization with exceptional precision. However, its application has largely been limited to cultured cells. In this research, we refined sample preparation protocols for 3D MINFLUX imaging in fixed brain tissue, focusing on mitochondrial distribution within dendritic spines and engram cells of the dentate gyrus. Probing single molecules reveals that mitochondrial inner membrane proteins reorganize during synaptic plasticity in dendritic spines of engram cells. Using 3D MINFLUX nanoscopy, we identified a significant redistribution of α-F1-ATP synthase, correlating with learning-related activities. This redistribution suggests a pivotal role for polarized ATP synthesis near the postsynaptic zone in modulating synaptic plasticity and memory consolidation. Dual-color 3D MINFLUX imaging uncovered distinct mitochondrial reorganization patterns involving both inner and outer membranes in dendritic spines. These patterns, induced by plasticity signals, persist for up to 12 h in neuronal cultures, highlighting distinct regulatory mechanisms governing mitochondrial proteins during plasticity. These findings provide new insights into the molecular mechanisms underlying synaptic plasticity and demonstrate the transformative potential of 3D MINFLUX imaging for studying neuronal processes in the brain.</p>

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Polarized ATP synthase in synaptic mitochondria induced by learning and plasticity signals

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Yi Hu,
  • Xi Wang,
  • Kaiyuan Liu,
  • Songhai Xiong,
  • Bing Cai,
  • Ji-Song Guan,
  • Min Gu,
  • Hong Xie

摘要

MINFLUX is a cutting-edge single-molecule localization microscopy technology that surpasses the conventional diffraction limit, enabling nanostructure visualization with exceptional precision. However, its application has largely been limited to cultured cells. In this research, we refined sample preparation protocols for 3D MINFLUX imaging in fixed brain tissue, focusing on mitochondrial distribution within dendritic spines and engram cells of the dentate gyrus. Probing single molecules reveals that mitochondrial inner membrane proteins reorganize during synaptic plasticity in dendritic spines of engram cells. Using 3D MINFLUX nanoscopy, we identified a significant redistribution of α-F1-ATP synthase, correlating with learning-related activities. This redistribution suggests a pivotal role for polarized ATP synthesis near the postsynaptic zone in modulating synaptic plasticity and memory consolidation. Dual-color 3D MINFLUX imaging uncovered distinct mitochondrial reorganization patterns involving both inner and outer membranes in dendritic spines. These patterns, induced by plasticity signals, persist for up to 12 h in neuronal cultures, highlighting distinct regulatory mechanisms governing mitochondrial proteins during plasticity. These findings provide new insights into the molecular mechanisms underlying synaptic plasticity and demonstrate the transformative potential of 3D MINFLUX imaging for studying neuronal processes in the brain.