黏附介导的机械信号转导力促进线粒体激素。
Adhesion-mediated mechanosignaling forces mitohormesis.
机构信息
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Molecular & Cellular Biology, Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94597, USA.
出版信息
Cell Metab. 2021 Jul 6;33(7):1322-1341.e13. doi: 10.1016/j.cmet.2021.04.017. Epub 2021 May 20.
Abstract
Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues. Here, we demonstrate that cells sense the physical properties of the extracellular matrix and activate a mitochondrial stress response that adaptively tunes mitochondrial function via solute carrier family 9 member A1-dependent ion exchange and heat shock factor 1-dependent transcription. Overall, our data indicate that adhesion-mediated mechanosignaling may play an unappreciated role in the altered mitochondrial functions observed in aging and cancer.
摘要
线粒体通过产生支持生命所需的能量和执行程序性细胞死亡所需的信号来控制真核细胞命运。已知生化环境会影响线粒体功能，并导致与癌症和衰老相关疾病中功能失调的线粒体表型有关。然而，细胞外基质的物理特性在癌变和衰老组织中也会发生改变。在这里，我们证明细胞感知细胞外基质的物理特性，并激活线粒体应激反应，通过溶质载体家族 9 成员 A1 依赖性离子交换和热休克因子 1 依赖性转录来适应性地调节线粒体功能。总的来说，我们的数据表明，黏附介导的机械信号可能在衰老和癌症中观察到的改变的线粒体功能中发挥了未被重视的作用。
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