摘要
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 complexⅡ,or succinate dehydrogenase(SDH),is regarded as a central regulator of respiratory adaptation and metabolic reprogramming in various stimuli and abnormalities.Four subunits of complexⅡare considered as tumor suppressors,whose mutations are associated with various type of cancer.However,little is known how complexⅡregulates cell proliferation.2-Thenoyltrifluoroacetone(TTFA),an inhibitor of mitochondrial complexⅡ,and SDHB shRNA were used to abolish the activity of complexⅡin cell lines.Inhibition the activity of complexⅡby TTFA treatment or knockdown of SDHB could trigger mitochondrial fragmentation and subsequently mitophagy.We also found that inhibition of complexⅡalso increased the glucose consumption and the lactate production which termed as Warburg effect.Despite of these,complexⅡdysfunction showed negative regulation to cell proliferation.Collectively,complexⅡis a potential target to induce mitophagy and inhibit cell proliferation.
作者
穆成龙
贺丽群
王家乐
赵田
朱玉山
陈佺
MU Cheng-Long;HE Li-Qun;WANG Jia-Le;ZHAO Tian;ZHU Yu-Shan;CHEN Quan(State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Protein Science,College of Life Sciences,Nankai University,Tianjin 300071,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2020年第11期1183-1190,共8页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(91754114)
中华人民共和国科学技术部基金(2019YFA0508600)资助项目。
