Mechanical ventilation triggers abnormal mitochondrial dynamics and morphology in the diaphragm
Mechanical ventilation triggers abnormal mitochondrial dynamics and morphology in the diaphragm
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DOI：
10.1152/japplphysiol.00873.2014
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发表时间：
2015-05-01
影响因子：
3.3
通讯作者：
Petrof, Basil J.
中科院分区：
文献类型：
--
作者：
Picard, Martin;Azuelos, Ilan;Petrof, Basil J.
膈肌是一种独特的骨骼肌，设计为在整个生命过程中有节奏地活动，因此通过机械通气（MV）的医疗干预使其持续失活代表了进化方面的意外生理状态。在开始MV后的短时间内，隔膜发生肌肉萎缩、损伤和力量减弱，其中许多特征似乎是由线粒体功能障碍引起的。值得注意的是，在响应代谢扰动，线粒体融合，分裂，并与相邻的细胞器相互作用，以重塑其形状和功能特性的过程统称为线粒体动力学。使用定量电子显微镜的方法，在这里，我们表明，隔膜收缩不活动引起6小时的MV在小鼠中导致肌原纤维间（IMF），但不是肌膜下（SS）线粒体的碎片。此外，相邻的细胞器膜之间的物理相互作用不太丰富的IMF线粒体在MV。的profusion蛋白Mfn2和OPA1没有变化，而丰度和激活状态的profission蛋白Drp1的隔膜MV后增加。总的来说，我们的研究结果表明，线粒体形态异常的特点是过度分裂碎片代表早期事件在MV，这可能有助于线粒体功能障碍，适应不良的信号，以及相关的膈肌收缩功能障碍的快速发作。
The diaphragm is a unique skeletal muscle designed to be rhythmically active throughout life, such that its sustained inactivation by the medical intervention of mechanical ventilation (MV) represents an unanticipated physiological state in evolutionary terms. Within a short period after initiating MV, the diaphragm develops muscle atrophy, damage, and diminished strength, and many of these features appear to arise from mitochondrial dysfunction. Notably, in response to metabolic perturbations, mitochondria fuse, divide, and interact with neighboring organelles to remodel their shape and functional properties-a process collectively known as mitochondrial dynamics. Using a quantitative electron microscopy approach, here we show that diaphragm contractile inactivity induced by 6 h of MV in mice leads to fragmentation of intermyofibrillar (IMF) but not subsarcolemmal (SS) mitochondria. Furthermore, physical interactions between adjacent organellar membranes were less abundant in IMF mitochondria during MV. The profusion proteins Mfn2 and OPA1 were unchanged, whereas abundance and activation status of the profission protein Drp1 were increased in the diaphragm following MV. Overall, our results suggest that mitochondrial morphological abnormalities characterized by excessive fission-fragmentation represent early events during MV, which could potentially contribute to the rapid onset of mitochondrial dysfunction, maladaptive signaling, and associated contractile dysfunction of the diaphragm.