Effects of acute cigarette smoke concentrate exposure on mitochondrial energy transfer in fast- and slow-twitch skeletal muscle.
Effects of acute cigarette smoke concentrate exposure on mitochondrial energy transfer in fast- and slow-twitch skeletal muscle.
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急性香烟烟雾浓度暴露对快肌和慢肌骨骼肌线粒体能量转移的影响。
DOI：
10.1016/j.bbabio.2023.148973
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Layec,Gwenael
中科院分区：
文献类型：
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作者：
Decker,StephenT;Alexandrou-Majaj,Nadia;Layec,Gwenael
香烟烟雾诱导的骨骼肌线粒体功能障碍的机制仍然知之甚少。因此，本研究旨在研究香烟烟雾对具有不同代谢特征的骨骼肌透化肌纤维中线粒体能量转移的影响。使用高分辨率呼吸测定法，在急性暴露于香烟烟雾浓缩物（CSC）的C57 BL/6小鼠（n= 11）的快肌和慢肌纤维中评估电子传递链（ETC）容量、ADP转运和ADP呼吸控制。CSC减少了白色腓肠肌（对照组：45.4 ± 11.2 pmolO2.s−1.mg− 1和CSC：27.5 ± 12.0 pmolO2.s−1.mg−1;p= 0.01）和比目鱼肌（对照组：63.0 ± 23.8 pmolO2.s−1.mg− 1和CSC：44.6 ± 11.1 pmolO2.s−1.mg−1;p= 0.04）中复合物I驱动的呼吸。相比之下，CSC对复合体II相关呼吸的影响增加了其对白色腓肠肌肌肉呼吸能力的相对贡献。CSC在两种肌肉中均显著抑制ETC的最大呼吸活动。此外，依赖于ADP/ATP跨线粒体膜转运的呼吸率在白色腓肠肌中被CSC显著损害（对照：-70 ± 18%; CSC：-28 ± 10%;p< 0.001），但在比目鱼肌中不被CSC显著损害（对照：47 ± 16%; CSC：31 ± 7%;p= 0.08）。CSC还显著损害了两种肌肉中的线粒体热力学偶联。我们的研究结果强调，急性CSC暴露直接抑制透化肌纤维中的氧化磷酸化。这种效应是由呼吸复合物中的电子转移的显著扰动介导的，特别是在复合物I中，在快肌和慢肌中。与此相反，CSC诱导的ADP/ATP跨线粒体膜交换的抑制是纤维类型特异性的，对快缩肌有很大的影响。
The mechanisms underlying cigarette smoke-induced mitochondrial dysfunction in skeletal muscle are still poorly understood. Accordingly, this study aimed to examine the effects of cigarette smoke on mitochondrial energy transfer in permeabilized muscle fibers from skeletal muscles with differing metabolic characteristics. The electron transport chain (ETC) capacity, ADP transport, and respiratory control by ADP were assessed in fast- and slow-twitch muscle fibers from C57BL/6 mice (n= 11) acutely exposed to cigarette smoke concentrate (CSC) using high-resolution respirometry. CSC decreased complex I-driven respiration in the white gastrocnemius (CONTROL:45.4 ± 11.2 pmolO2.s−1.mg−1and CSC:27.5 ± 12.0 pmolO2.s−1.mg−1;p= 0.01) and soleus (CONTROL:63.0 ± 23.8 pmolO2.s−1.mg−1and CSC:44.6 ± 11.1 pmolO2.s−1.mg−1;p= 0.04). In contrast, the effect of CSC on Complex II-linked respiration increased its relative contribution to muscle respiratory capacity in the white gastrocnemius muscle. The maximal respiratory activity of the ETC was significantly inhibited by CSC in both muscles. Furthermore, the respiration rate dependent on the ADP/ATP transport across the mitochondrial membrane was significantly impaired by CSC in the white gastrocnemius (CONTROL:-70 ± 18 %; CSC:-28 ± 10 %;p< 0.001), but not the soleus (CONTROL:47 ± 16 %; CSC:31 ± 7 %;p= 0.08). CSC also significantly impaired mitochondrial thermodynamic coupling in both muscles. Our findings underscore that acute CSC exposure directly inhibits oxidative phosphorylation in permeabilized muscle fibers. This effect was mediated by significant perturbations of the electron transfer in the respiratory complexes, especially at complex I, in both fast and slow twitch muscles. In contrast, CSC-induced inhibition of the exchange of ADP/ATP across the mitochondrial membrane was fiber-type specific, with a large effect on fast-twitch muscles.