Feofilaktova Tatiana, Kushnireva Liliia, Segal Menahem, Korkotian Eduard
Faculty of Biology, Perm State University, Perm, Russia.
Department of Immunology and Regenerative Biology, The Weizmann Institute, Rehovot, Israel.
Front Mol Neurosci. 2025 Jul 21;18:1621070. doi: 10.3389/fnmol.2025.1621070. eCollection 2025.
While the overall ATP level in neurons remains relatively stable, local fluctuations in synaptic compartments - driven by synaptic potentials - necessitate rapid ATP adjustments. The energy supply for synaptic activity in neurons must be under precise homeostatic control: increased ATP consumption in active synapses requires continuous replenishment, whereas in periods of inactivity, excess ATP production may occur. Overproduction of ATP in thousands of individual synapses is metabolically wasteful, while underproduction threatens to disrupt molecular cascades associated with ongoing synaptic bursts, ion homeostasis, protein synthesis, and neural plasticity. Fine-tuned regulation of ATP synthesis must therefore be controlled locally and dynamically, ensuring metabolic efficiency while preventing disruptions in synaptic bursts, ion homeostasis, and neuronal plasticity. This review summarizes the intricate molecular mechanisms through which mitochondria (MT) interact with their postsynaptic environment to maintain energy balance. We examined the fundamental features of mitochondria in conjunction with their unique properties and roles in nervous tissue, highlighting their ability to dynamically adjust energy production based on local demand rather than maintaining a strictly uniform ATP output. The regulation of ATP synthesis may involve mitochondrial transport, fusion, and fission, as well as changes in mitochondrial shape and molecular structure. This review describes the activity of ATP synthase, the mitochondrial calcium uniporter and other signaling cascades in the context of their uneven distribution within mitochondria. Furthermore, we discuss rapid calcium influxes from postsynaptic membranes and the endoplasmic reticulum into mitochondria-associated membranes (MAMs), their buffering mechanisms, and the generation of dynamic responses. We focus on the role of calcium ion (Ca) as a precise regulator of ATP production, particularly in mitochondria located near synaptic regions, where it ensures an adequate energy supply for local activity. Overall, we propose potential pathways of interaction between mitochondria and their postsynaptic microdomains. Given that some of the mechanisms discussed remain hypothetical, we emphasize the urgent need for experimental validation to refine understanding of mitochondrial function in synaptic transmission.
虽然神经元中的总体ATP水平保持相对稳定，但由突触电位驱动的突触小室中的局部波动需要快速调整ATP。神经元中突触活动的能量供应必须处于精确的稳态控制之下：活跃突触中ATP消耗的增加需要持续补充，而在不活跃时期，可能会出现ATP产生过多的情况。数千个单个突触中ATP的过度产生在代谢上是浪费的，而产生不足则可能会破坏与正在进行的突触爆发、离子稳态、蛋白质合成和神经可塑性相关的分子级联反应。因此，ATP合成的微调调节必须在局部和动态水平上进行控制，以确保代谢效率，同时防止突触爆发、离子稳态和神经元可塑性受到干扰。本综述总结了线粒体（MT）与其突触后环境相互作用以维持能量平衡的复杂分子机制。我们结合线粒体在神经组织中的独特性质和作用，研究了其基本特征，强调了它们能够根据局部需求动态调整能量产生，而不是维持严格均匀的ATP输出。ATP合成的调节可能涉及线粒体的运输、融合和裂变，以及线粒体形状和分子结构的变化。本综述描述了ATP合酶、线粒体钙单向转运体和其他信号级联反应在其在线粒体内分布不均的情况下的活性。此外，我们讨论了从突触后膜和内质网到线粒体相关膜（MAM）的快速钙内流、它们的缓冲机制以及动态反应的产生。我们重点关注钙离子（Ca）作为ATP产生精确调节因子的作用，特别是在突触区域附近的线粒体中，它确保为局部活动提供充足的能量供应。总体而言，我们提出了线粒体与其突触后微区之间潜在的相互作用途径。鉴于所讨论的一些机制仍然是假设性的，我们强调迫切需要进行实验验证，以完善对突触传递中线粒体功能的理解。
