钙离子 (Ca2+) 在调节正常细胞和癌细胞的众多细胞功能（包括代谢和生长）方面发挥着关键作用。因此，Ca2 信号传导是细胞命运的重要决定因素，影响细胞的存活和死亡。这些细胞内信号容易受到各种因素的调节，包括细胞外环境的变化，从而导致机械变化。然而，细胞外基质 (ECM) 硬度变化对细胞内 Ca2 信号传导的影响仍未得到充分研究。在这项研究中，我们的目的是阐明通过线粒体调节 Ca2+ 的机制，这对于 Ca2+ 稳态至关重要。我们通过使用基因编码的生物传感器同时对活细胞中的线粒体和内质网 (ER) 进行成像，研究了 Ca2 调节机制如何适应不同水平的 ECM 硬度。我们的研究结果表明，细胞内微管蛋白促进的电压依赖性阴离子通道 1 (VDAC1) 对线粒体 Ca2 的摄取受到 ECM 硬度的影响。解开各种条件下的这些 Ca2 调节机制，为推进涉及 Ca2 信号传导的生物医学研究提供了新的视角。© 2024 作者。由 Informa UK Limited 出版，以 Taylor 名义进行交易

Calcium ions (Ca2+) play pivotal roles in regulating numerous cellular functions, including metabolism and growth, in normal and cancerous cells. Consequently, Ca2+ signaling is a vital determinant of cell fate and influences both cell survival and death. These intracellular signals are susceptible to modulation by various factors, including changes in the extracellular environment, which leads to mechanical alterations. However, the effect of extracellular matrix (ECM) stiffness variations on intracellular Ca2+ signaling remains underexplored. In this study, we aimed to elucidate the mechanisms of Ca2+ regulation through the mitochondria, which are crucial to Ca2+ homeostasis. We investigated how Ca2+ regulatory mechanisms adapt to different levels of ECM stiffness by simultaneously imaging the mitochondria and endoplasmic reticulum (ER) in live cells using genetically encoded biosensors. Our findings revealed that the uptake of mitochondrial Ca2+ through Voltage-Dependent Anion Channel 1 (VDAC1), facilitated by intracellular tubulin, is influenced by ECM stiffness. Unraveling these Ca2+ regulatory mechanisms under various conditions offers a novel perspective for advancing biomedical studies involving Ca2+ signaling.© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.