论文部分内容阅读
线粒体复合体Ⅱ,也被称为琥珀酸脱氢酶,参与线粒体呼吸作用及代谢重编程的调控过程.复合体Ⅱ由4个亚基构成,其突变与肿瘤的发生密切相关.本文探讨复合体Ⅱ与线粒体自噬调控及细胞增殖之间的关系.实验采用复合体Ⅱ的特异性抑制剂TTFA或敲除复合体Ⅱ的B亚基(SDHB)使其功能缺失.结果发现,复合体Ⅱ功能的缺失显著引起线粒体形态的片段化进而发生线粒体自噬,导致线粒体蛋白水平减少,抑制ATP生成;由于线粒体功能受到抑制,细胞葡萄糖消耗及乳酸产生水平增加,并显著抑制细胞的细胞的增殖.综上所述,复合体Ⅱ功能缺失可能通过调控线粒体自噬而影响细胞增殖,从而在肿瘤发生中起重要作用.“,”Mitochondrial complex Ⅱ,or succinate dehydrogenase (SDH),is regarded as a central regulator of respiratory adaptation and metabolic reprogramming in various stimuli and abnormalities.Four subunits of complex Ⅱ are considered as tumor suppressors,whose mutations are associated with various type of cancer.However,little is known how complex Ⅱ regulates cell proliferation.2-Thenoyltrifluoroacetone (TTFA),an inhibitor of mitochondrial complex Ⅱ,and SDHB shRNA were used to abolish the activity of complex Ⅱ in cell lines.Inhibition the activity of complex Ⅱ by TTFA treatment or knockdown of SDHB could trigger mitochondrial fragmentation and subsequently mitophagy.We also found that inhibition of complex Ⅱ also increased the glucose consumption and the lactate production which termed as Warburg effect.Despite of these,complex Ⅱ dysfunction showed negative regulation to cell proliferation.Collectively,complex Ⅱ is a potential target to induce mitophagy and inhibit cell proliferation.