Department of Kinesiology, University of Massachusetts Amherst, USA.
Department of Psychology and Brain Sciences, University of Massachusetts Amherst, USA.
Biochim Biophys Acta Bioenerg. 2023 Aug 1;1864(3):148973. doi: 10.1016/j.bbabio.2023.148973. Epub 2023 Mar 25.
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 pmolO.s.mg and CSC:27.5 ± 12.0 pmolO.s.mg; p = 0.01) and soleus (CONTROL:63.0 ± 23.8 pmolO.s.mg and CSC:44.6 ± 11.1 pmolO.s.mg; 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.
香烟烟雾引起骨骼肌线粒体功能障碍的机制仍知之甚少。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通透性纤维中线粒体能量传递的影响。使用高分辨率呼吸仪，在急性暴露于香烟烟雾浓缩物（CSC）的 C57BL/6 小鼠的快肌和慢肌纤维中评估电子传递链（ETC）能力、ADP 转运和 ADP 控制的呼吸作用。CSC 降低了白色比目鱼肌（CONTROL：45.4±11.2 pmolO.s.mg 和 CSC：27.5±12.0 pmolO.s.mg；p=0.01）和比目鱼肌（CONTROL：63.0±23.8 pmolO.s.mg 和 CSC：44.6±11.1 pmolO.s.mg；p=0.04）中复合物 I 驱动的呼吸作用。相比之下，CSC 对复合物 II 连接的呼吸作用的影响增加了其对白色比目鱼肌呼吸能力的相对贡献。ETC 的最大呼吸活性在两种肌肉中均被 CSC 显著抑制。此外，CSC 显著损害了白色比目鱼肌中线粒体膜 ADP/ATP 转运依赖的呼吸率（CONTROL：-70±18%；CSC：-28±10%；p<0.001），但对比目鱼肌没有影响（CONTROL：47±16%；CSC：31±7%；p=0.08）。CSC 还显著损害了两种肌肉的线粒体热力学偶联。我们的研究结果强调了急性 CSC 暴露直接抑制通透性纤维中的氧化磷酸化。这种作用是通过呼吸复合物中电子传递的显著扰动介导的，特别是在快肌和慢肌中的复合物 I。相比之下，CSC 诱导的 ADP/ATP 跨线粒体膜交换抑制是纤维型特异性的，对快肌有很大影响。
