Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Mitochondrion. 2020 May;52:8-19. doi: 10.1016/j.mito.2020.02.002. Epub 2020 Feb 8.
Mitochondrial dysfunction occurring in response to cellular perturbations can include altered mitochondrial motility and bioenergetic function having intracellular heterogeneity. Exogenous mitochondrial directed therapy may correct these dysfunctions. Using in vitro approaches, we find that cell perturbations induced by rapid decompression from hyperbaric conditions with specific gas exposures has differential effects on mitochondrial motility, inner membrane potential, cellular respiration, reactive oxygen species production, impaired maintenance of cell shape and altered intracellular distribution of bioenergetic capacity in perinuclear and cell peripheral domains. Addition of a first-generation cell-permeable succinate prodrug to support mitochondrial function has positive overall effects in blunting the resultant bioenergy responses. Our results with this model of perturbed cell function induced by rapid decompression indicate that alterations in bioenergetic state are partitioned within the cell, as directly assessed by a combination of mitochondrial respiration and dynamics measurements. Reductions in the observed level of dysfunction produced can be achieved with application of the cell-permeable succinate prodrug.
线粒体功能障碍是细胞扰动的一种反应，包括改变线粒体的运动和生物能量功能，具有细胞内异质性。外源性线粒体靶向治疗可能纠正这些功能障碍。通过体外方法，我们发现，快速减压从高压条件下特定气体暴露诱导的细胞扰动对线粒体运动、内膜电位、细胞呼吸、活性氧产生、细胞形状维持受损以及细胞内生物能量能力在核周和细胞周围区域的分布产生不同的影响。添加第一代细胞通透性琥珀酸前药来支持线粒体功能具有积极的整体效果，能减轻由此产生的生物能量反应。我们用快速减压引起的受扰细胞功能的模型得到的结果表明，生物能状态的改变在细胞内进行分区，如通过线粒体呼吸和动力学测量的组合直接评估。通过应用细胞通透性琥珀酸前药，可以减少观察到的功能障碍水平。
