Modulation of mitochondrial function by hydrogen peroxide
Modulation of mitochondrial function by hydrogen peroxide
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DOI：
10.1074/jbc.m100320200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Szweda, LI
中科院分区：
文献类型：
--
作者：
Nulton-Persson, AC;Szweda, LI
在正常的细胞代谢过程中，线粒体电子传递导致超氧阴离子（O-2）和随后的过氧化氢（H2 O2）的形成。由于H2 O2在某些生理和病理生理条件下浓度增加，并且可以氧化修饰细胞组分，因此了解线粒体对H2 O2的反应至关重要。在本研究中，用H2 O2处理离体大鼠心脏线粒体导致状态3 NADH相关呼吸的下降和随后的恢复。H2 O2诱导的NADH水平的变化与状态3呼吸速率的变化密切平行。电子传递链复合物和Krebs循环酶的评估表明，α-酮戊二酸脱氢酶（KGDH），琥珀酸脱氢酶（SDH）和乌头酸酶易受H2 O2灭活。特别重要的是，KGDH和SDH活性恢复到对照水平，同时恢复状态3呼吸。H_2O_2与KGDH和SDH的直接作用不是失活的原因。此外，单独去除H2 O2不足以使酶再活化，除非线粒体保持完整，否则酶活性不会恢复。KGDH和SDH对H2 O2介导的失活的敏感性和失活的可逆性表明H2 O2在KGDH和SDH的调节中具有潜在的作用。
During normal cellular metabolism, mitochondrial electron transport results in the formation of superox ide anion (O-2) and subsequently hydrogen peroxide (H2O2). Because H2O2 increases in concentration under certain physiologic and pathophysiologic conditions and can oxidatively modify cellular components, it is critical to understand the response of mitochondria to H2O2. In the present study, treatment of isolated rat heart mitochondria with H2O2 resulted in a decline and subsequent recovery of state 3 NADH-linked respiration. Alterations in NADH levels induced by H2O2 closely paralleled changes in the rate of state 3 respiration. Assessment of electron transport chain complexes and Krebs cycle enzymes revealed that alpha -ketoglutarate dehydrogenase (KGDH), succinate dehydrogenase (SDH), and aconitase were susceptible to H2O2 inactivation. Of particular importance, KGDH and SDH activity returned to control levels, concurrent with the recovery of state 3 respiration. Inactivation is not because of direct interaction of H2O2 with KGDH and SDH. In addition, removal of H2O2 alone is not sufficient for reactivation, Enzyme activity does not recover unless mitochondria remain intact. The sensitivity of KGDH and SDH to H2O2-mediated inactivation and the reversible nature of inactivation suggest a potential role for H2O2 in the regulation of KGDH and SDH.