Mitochondrial respiration is sensitive to cytoarchitectural breakdown.
Mitochondrial respiration is sensitive to cytoarchitectural breakdown.
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线粒体呼吸对细胞结构破坏敏感。
DOI：
10.1039/c6ib00192k
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Eckmann,DavidM
中科院分区：
文献类型：
--
作者：
Kandel,Judith;Angelin,AlessiaA;Wallace,DouglasC;Eckmann,DavidM
大量的研究表明，细胞线粒体和细胞骨架破坏是相关的，但很少有研究直接调查两者之间的因果关系。我们以前证明，抑制微管和微丝聚合影响成纤维细胞在全细胞水平上的线粒体运动。由于线粒体运动可以指示线粒体功能，我们现在进一步表征这些细胞骨架抑制剂对线粒体电位、形态和呼吸的影响。我们发现，虽然他们没有降低线粒体内膜电位，细胞骨架毒素诱导基础线粒体呼吸显着下降。在某些情况下，基础呼吸仅在用钙离子载体A23187预处理细胞以强调线粒体功能后受到影响。在大多数情况下，线粒体形态保持不受影响，但极端的微丝解聚或组合的中间剂量的微管和微丝毒素导致线粒体长度减少。有趣的是，这两种特定的暴露不会影响未用A23187致敏的细胞中的线粒体呼吸，表明线粒体形态和呼吸之间的相互作用。在所有情况下，诱导最大呼吸减少对照组和实验组之间的差异，表明减少基础呼吸起源于一个很大程度上选择性的，而不是病理性症状的细胞骨架损伤。然而，生存力实验表明，即使这种类型的呼吸减少也可能与细胞死亡有关。
An abundance of research suggests that cellular mitochondrial and cytoskeletal disruption are related, but few studies have directly investigated causative connections between the two. We previously demonstrated that inhibiting microtubule and microfilament polymerization affects mitochondrial motility on the whole-cell level in fibroblasts. Since mitochondrial motility can be indicative of mitochondrial function, we now further characterize the effects of these cytoskeletal inhibitors on mitochondrial potential, morphology and respiration. We found that although they did not reduce mitochondrial inner membrane potential, cytoskeletal toxins induced significant decreases in basal mitochondrial respiration. In some cases, basal respiration was only affected after cells were pretreated with the calcium ionophore A23187 in order to stress mitochondrial function. In most cases, mitochondrial morphology remained unaffected, but extreme microfilament depolymerization or combined intermediate doses of microtubule and microfilament toxins resulted in decreased mitochondrial lengths. Interestingly, these two particular exposures did not affect mitochondrial respiration in cells not sensitized with A23187, indicating an interplay between mitochondrial morphology and respiration. In all cases, inducing maximal respiration diminished differences between control and experimental groups, suggesting that reduced basal respiration originates as a largely elective rather than pathological symptom of cytoskeletal impairment. However, viability experiments suggest that even this type of respiration decrease may be associated with cell death.