Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels.
Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels.
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DOI：
10.1016/j.bbrc.2012.05.055
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发表时间：
2012-06-08
影响因子：
3.1
通讯作者：
Van Remmen H
中科院分区：
文献类型：
--
作者：
Lustgarten MS;Bhattacharya A;Muller FL;Jang YC;Shimizu T;Shirasawa T;Richardson A;Van Remmen H
线粒体复合体I以前被证明只向线粒体基质释放超氧化物，而复合体III向基质和胞浆释放超氧化物。研究表明，络合物III产生的超氧化物通过电压依赖的阴离子通道(VDAC)离开线粒体。为了测试复合体I衍生的、线粒体基质导向的超氧化物歧化酶是否可以释放到细胞质中，我们测量了从野生型和遗传改变为MnSOD活性缺陷的小鼠线粒体中超氧化物歧化酶的生成(TnIFastCreSod2fl/fl)。在主要由谷氨酸/苹果酸+鱼藤酮(GM+R)产生超氧化物的实验条件下，MnSOD缺陷的线粒体释放的超氧化物歧化能力是野生型小鼠线粒体的~4倍。外源铜锌超氧化物歧化酶完全阻断EPR诱导的GM+R信号，证实线粒体释放超氧化物歧化。加入VDAC抑制剂DIDS可显著降低呼吸GM+R的线粒体的超氧化物歧化释放量(~75%)。相反，抑制线粒体通透性转换孔的基质面和内膜阴离子通道等可能的超氧化物出口内膜部位并不能减少GM+R存在时线粒体的超氧化物歧化释放量。这些数据支持这一概念，即复杂的I-衍生线粒体超氧化物释放确实发生，并且这种释放的大部分通过VDAC发生。
Mitochondrial complex I has previously been shown to release superoxide exclusively towards the mitochondrial matrix, whereas complex III releases superoxide to both the matrix and the cytosol. Superoxide produced at Complex III has been shown to exit the mitochondria through voltage dependent anion channels (VDAC). To test whether complex I-derived, mitochondrial matrix-directed superoxide can be released to the cytosol, we measured superoxide generation in mitochondria isolated from wild type and from mice genetically altered to be deficient in MnSOD activity (TnIFastCreSod2fl/fl). Under experimental conditions that produce superoxide primarily by complex I (glutamate/malate plus rotenone, GM+R), MnSOD-deficient mitochondria release ~4-fold more superoxide than mitochondria isolated from wild type mice. Exogenous CuZnSOD completely abolished the EPR-derived GM+R signal in mitochondria isolated from both genotypes, evidence that confirms mitochondrial superoxide release. Addition of the VDAC inhibitor DIDS significantly reduced mitochondrial superoxide release (~75%) in mitochondria from either genotype respiring on GM+R. Conversely, inhibition of potential inner membrane sites of superoxide exit, including the matrix face of the mitochondrial permeability transition pore and the inner membrane anion channel did not reduce mitochondrial superoxide release in the presence of GM+R in mitochondria isolated from either genotype. These data support the concept that complex I-derived mitochondrial superoxide release does indeed occur and that the majority of this release occurs through VDACs.
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影响因子：
3
作者：
Mannella, CA
通讯作者：
Mannella, CA
影响因子：
3.5
作者：
ShoshanBarmatz, V;Hadad, N;Heilmeyer, LMG
通讯作者：
Heilmeyer, LMG
影响因子：
4.3
作者：
Fato, Romana;Bergamini, Christian;Bortolus, Marco;Maniero, Anna Lisa;Leoni, Serena;Ohnishi, Tomoko;Lenaz, Giorgio
通讯作者：
Lenaz, Giorgio
DOI：
10.1016/s0960-0760(99)00056-4
发表时间：
1999-04-01
影响因子：
4.1
作者：
Culty, M;Li, H;Papadopoulos, V
通讯作者：
Papadopoulos, V
DOI：
10.1073/pnas.89.8.3170
发表时间：
1992-04-15
影响因子：
11.1
作者：
MCENERY, MW;SNOWMAN, AM;SNYDER, SH
通讯作者：
SNYDER, SH