Mitochondrial substrate level phosphorylation is essential for growth of procyclic Trypanosoma brucei
Mitochondrial substrate level phosphorylation is essential for growth of procyclic Trypanosoma brucei
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DOI：
10.1074/jbc.m205776200
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发表时间：
2002-09-06
影响因子：
4.8
通讯作者：
Schneider, A
中科院分区：
文献类型：
--
作者：
Bochud-Allemann, N;Schneider, A
柠檬酸和乙酸：琥珀酸CoA转移酶/琥珀酰CoA合成酶循环中琥珀酰CoA合成酶催化的氧化磷酸化和底物水平磷酸化有助于前环布氏锥虫的线粒体ATP合成。后一种途径对锥虫是特异性的，但也在氢化酶体中发现。在organello ATP的生产进行了研究，在野生型和RNA干扰细胞系消融的关键酶的三个途径。结果表明：（1）直接证明了乙酸：琥珀酸CoA转移酶/琥珀酰CoA合成酶循环中ATP的产生。2)琥珀酸脱氢酶似乎是线粒体底物电子进入呼吸链的唯一入口点;然而，其活性可以被消融而不引起生长表型。3)原环木T.布氏杆菌不受功能性柠檬酸或乙酸：琥珀酸CoA转移酶/琥珀酰-CoA合成酶循环缺失的影响。然而，在同一细胞系中两种途径的中断导致生长停滞。总之，这些结果表明，与柠檬酸循环相关或与乙酸产生相关的非氧依赖性底物水平磷酸化对于原环T的生长是必不可少的。布氏杆菌，这种情况可能反映了昆虫宿主对部分缺氧条件的适应。
Oxidative phosphorylation and substrate level phosphorylation catalyzed by succinyl-CoA synthetase found in the citric acid and the acetate:succinate CoA transferase/succinyl-CoA synthetase cycle contribute to mitochondrial ATP synthesis in procyclic Trypanosoma brucei. The latter pathway is specific for trypanosome but also found in hydrogenosomes. In organello ATP production was studied in wild-type and in RNA interference cell lines ablated for key enzymes of each of the three pathways. The following results were obtained: 1) ATP production in the acetate:succinate CoA transferase/succinyl-CoA synthetase cycle was directly demonstrated. 2) Succinate dehydrogenase appears to be the only entry point for electrons of mitochondrial substrates into the respiratory chain; however, its activity could be ablated without causing a growth phenotype. 3) Growth of procyclic T. brucei was not affected by the absence of either a functional citric acid or the acetate: succinate CoA transferase/succinyl-CoA synthetase cycle. However, interruption of both pathways in the same cell line resulted in a growth arrest. In summary, these results show that oxygen-independent substrate level phosphorylation either linked to the citric acid cycle or tied into acetate production is essential for growth of procyclic T. brucei, a situation that may reflect an adaptation to the partially hypoxic conditions in the insect host.