Novel interactions between mitochondrial superoxide dismutases and the electron transport chain.
Novel interactions between mitochondrial superoxide dismutases and the electron transport chain.
复制标题
DOI：
10.1111/acel.12144
复制
发表时间：
2013-12
期刊：
影响因子：
7.8
通讯作者：
Morgan PG
中科院分区：
文献类型：
--
作者：
Suthammarak W;Somerlot BH;Opheim E;Sedensky M;Morgan PG
控制衰老的过程仍然知之甚少。我们利用线虫中的突变，线虫，损害线粒体功能和清除活性氧物种(ROS)，以了解它们与寿命的关系。我们发现了线粒体超氧化物歧化酶(MtSOD)、超氧化物歧化酶-2和超氧化物歧化酶-3的作用和相互作用。两种超氧化物歧化酶均定位于线粒体超复合体I：III：IV。特异性地：1)降低复合体I和II的活性；复合体III和IV保持正常，2)延长复合体I缺陷动物的寿命，但不延长复合体II缺陷动物的寿命，并导致复杂III缺陷动物死亡，3)诱导可能的促炎反应。敲除一种可能是促炎介质的分子，可以非常显著地延长某些线粒体突变体的寿命和健康。电子传输链、ROS和寿命之间的关系是复杂的，线粒体功能缺陷与ROS清除机制有特定的相互作用。我们得出结论，mtSOD嵌入在I：III：IV超复合体中，稳定或局部保护它免受活性氧物种(ROS)的损害。这些结果呼吁改变通常的电子传输链功能、ROS释放、清除和补偿反应的相互作用模式。
The processes that control aging remain poorly understood. We have exploited mutants in the nematode, C. elegans, that compromise mitochondrial function and scavenging of reactive oxygen species (ROS) to understand their relation to lifespan. We discovered unanticipated roles and interactions of the mitochondrial superoxide dismutases (mtSODs), SOD-2 and SOD-3. Both SODs localize to mitochondrial supercomplex I:III:IV. Loss of SOD-2 specifically: 1) decreases the activities of complexes I and II; complexes III, and IV remain normal, 2) increases the lifespan of animals with a complex I defect, but not the lifespan of animals with a complex II defect, and kills an animal with a complex III defect, 3) induces a presumed pro-inflammatory response. Knockdown of a molecule that may be a pro-inflammatory mediator very markedly extends lifespan and health of certain mitochondrial mutants. The relationship between the electron transport chain, ROS and lifespan is complex, and defects in mitochondrial function have specific interactions with ROS scavenging mechanisms. We conclude that mtSODs are embedded within the supercomplex I:III:IV, and stabilize or locally protect it from reactive oxygen species (ROS) damage. The results call for a change in the usual paradigm for the interaction of electron transport chain function, ROS release, scavenging and compensatory responses.
登录
查看更多内容
影响因子：
7.4
作者：
Keaney, M;Matthijssens, F;Gems, D
通讯作者：
Gems, D
影响因子：
64.8
作者：
Ishii, N;Fujii, M;Suzuki, K
通讯作者：
Suzuki, K
影响因子：
3.5
作者：
Grad, LI;Lemire, BD
通讯作者：
Lemire, BD
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
影响因子：
4.8
作者：
Kayser, EB;Sedensky, MM;Hoppel, CL
通讯作者：
Hoppel, CL