It is a textbook definition that in the absence of oxygen or inhibition of the mitochondrial respiratory chain by pharmacologic or genetic means, hyper-reduction of the matrix pyridine nucleotide pool ensues due to impairment of complex I oxidizing NADH, leading to reductive stress. However, even under these conditions, the ketoglutarate dehydrogenase complex (KGDHC) is known to provide succinyl-CoA to succinyl-CoA ligase, thus supporting mitochondrial substrate-level phosphorylation (mSLP). Mindful that KGDHC is dependent on provision of NAD+, hereby sources of acute NADH oxidation are reviewed, namely i) mitochondrial diaphorases, ii) reversal of mitochondrial malate dehydrogenase, iii) reversal of the mitochondrial isocitrate dehydrogenase as it occurs under acidic conditions, iv) residual complex I activity and v) reverse operation of the malate-aspartate shuttle. The concept of NAD+ import through the inner mitochondrial membrane as well as artificial means of manipulating matrix NAD+/NADH are also discussed. Understanding the above mechanisms providing NAD+ to KGDHC thus supporting mSLP may assist in dampening mitochondrial dysfunction underlying neurological disorders encompassing impairment of the electron transport chain.

中文翻译：

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呼吸链功能异常期间线粒体NAD +的急性来源。

这是一本教科书的定义，在没有氧气或通过药理或遗传手段抑制线粒体呼吸链的情况下，由于复合物I氧化NADH的损伤而导致基质吡啶核苷酸库过度还原，从而导致还原压力。但是，即使在这些条件下，酮戊二酸脱氢酶复合物（KGDHC）也会为琥珀酰CoA连接酶提供琥珀酰CoA，从而支持线粒体底物水平的磷酸化（mSLP）。意识到KGDHC依赖于NAD +的提供，因此回顾了急性NADH氧化的来源，即i）线粒体心肌黄递酶，ii）线粒体苹果酸脱氢酶逆转，iii）线粒体异柠檬酸脱氢酶在酸性条件下发生逆转，iv）残留的复合物I活性，v）苹果酸-天冬氨酸穿梭的反向操作。还讨论了通过线粒体内膜导入NAD +的概念以及操纵基质NAD + / NADH的人工方法。理解向KGDHC提供NAD +从而支持mSLP的上述机制可能有助于减轻线粒体功能障碍，这是包括电子运输链受损在内的神经系统疾病的基础。