Oyanagi Eri, Yano Hiromi, Kato Yasuko, Fujita Hirofumi, Utsumi Kozo, Sasaki Junzo
Department of Cytology & Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Shikata, Okayama, Japan.
Cell Biochem Funct. 2008 Oct;26(7):778-86. doi: 10.1002/cbf.1506.
Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca(2+) transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation.
线粒体膜通透性转换（MPT）在各种细胞凋亡中起重要作用。经典类型的MPT的特征是钙（Ca2+）转运增加、膜去极化、肿胀以及对环孢菌素A敏感。在本研究中，我们使用大鼠肝脏分离的线粒体研究了左旋肉碱是否抑制油酸诱导的MPT。油酸诱导分离线粒体中的MPT，抑制内源性呼吸，引起膜去极化，并增加大幅度肿胀以及细胞色素c（Cyt. c）从线粒体的释放。左旋肉碱对于线粒体中油酸的β氧化是必不可少的，并且该反应需要ATP和辅酶A（CoA）。在ATP和CoA存在的情况下，左旋肉碱刺激油酸氧化并抑制油酸诱导的去极化、肿胀以及Cyt. c释放。左旋肉碱还有助于维持线粒体功能，线粒体功能会随着分离后时间的推移因游离脂肪酸的产生而降低。这些结果表明，左旋肉碱通过加速β氧化来维持线粒体功能并抑制油酸介导的MPT。
