Brown G C
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Biochim Biophys Acta. 2001 Mar 1;1504(1):46-57. doi: 10.1016/s0005-2728(00)00238-3.
Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a variety of means. Nanomolar concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Isolated mitochondria, cultured cells, isolated tissues and animals in vivo display respiratory inhibition by endogenously produced NO from constitutive isoforms of NO synthase (NOS), which may be largely mediated by NO inhibition of cytochrome oxidase. Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and reversibly inhibit their own cellular respiration and that of co-incubated cells due to NO inhibition of cytochrome oxidase, but after longer-term incubation result in irreversible inhibition of cellular respiration due to NO or its derivatives. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen.
一氧化氮（NO）及其衍生物通过多种方式抑制线粒体呼吸。在分离的细胞色素氧化酶、线粒体、神经末梢、培养细胞和组织中，纳摩尔浓度的NO会立即、特异性且可逆地与氧气竞争抑制细胞色素氧化酶。更高浓度的NO及其衍生物（过氧亚硝酸盐、二氧化氮或亚硝基硫醇）可导致呼吸链的不可逆抑制、解偶联、通透性转换和/或细胞死亡。分离的线粒体、培养细胞、分离的组织和体内动物表现出由一氧化氮合酶（NOS）组成型同工型内源性产生的NO引起的呼吸抑制，这可能主要由NO对细胞色素氧化酶的抑制介导。表达诱导型NOS（iNOS）的培养细胞可由于NO对细胞色素氧化酶的抑制而急性且可逆地抑制其自身的细胞呼吸以及共孵育细胞的呼吸，但在长期孵育后，由于NO或其衍生物导致细胞呼吸的不可逆抑制。因此，NO对细胞色素氧化酶的抑制可能参与呼吸速率及其对氧气亲和力的生理和/或病理调节。
