抑制线粒体复合体II诱导线粒体自噬影响细胞增殖的研究

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由四个亚基构成，其突变与肿瘤的发生密切相关。本论文探讨了复合体II与线粒体自噬调控及细胞增殖之间的关系。本实验采用复合体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。

Inhibition of mitochondrial complex II induces mitophagy and attenuates cell proliferation

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.