Gospodaryov Dmytro V
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka, 76018, Ivano-Frankivsk, Ukraine.
Biochim Biophys Acta Bioenerg. 2025 Apr 1;1866(2):149529. doi: 10.1016/j.bbabio.2024.149529. Epub 2024 Nov 28.
Alternative NADH dehydrogenase, also known as type II NADH dehydrogenase (NDH-2), catalyzes the same redox reaction as mitochondrial respiratory chain complex I. Specifically, it oxidizes reduced nicotinamide adenine dinucleotide (NADH) while simultaneously reducing ubiquinone to ubiquinol. However, unlike complex I, this enzyme is non-proton pumping, comprises of a single subunit, and is resistant to rotenone. Initially identified in bacteria, fungi and plants, NDH-2 was subsequently discovered in protists and certain animal taxa including sea squirts. The gene coding for NDH-2 is also present in the genomes of some annelids, tardigrades, and crustaceans. For over two decades, NDH-2 has been investigated as a potential substitute for defective complex I. In model organisms, NDH-2 has been shown to ameliorate a broad spectrum of conditions associated with complex I malfunction, including symptoms of Parkinson's disease. Recently, lifespan extension has been observed in animals expressing NDH-2 in a heterologous manner. A variety of mechanisms have been put forward by which NDH-2 may extend lifespan. Such mechanisms include the activation of pro-longevity pathways through modulation of the NAD/NADH ratio, decreasing production of reactive oxygen species (ROS) in mitochondria, or then through moderate increases in ROS production followed by activation of defense pathways (mitohormesis). This review gives an overview of the latest research on NDH-2, including the structural peculiarities of NDH-2, its inhibitors, its role in the pathogenicity of mycobacteria and apicomplexan parasites, and its function in bacteria, fungi, and animals.
替代NADH脱氢酶，也称为II型NADH脱氢酶（NDH-2），催化与线粒体呼吸链复合体I相同的氧化还原反应。具体而言，它氧化还原型烟酰胺腺嘌呤二核苷酸（NADH），同时将泛醌还原为泛醇。然而，与复合体I不同的是，这种酶不进行质子泵转运，由单个亚基组成，并且对鱼藤酮具有抗性。NDH-2最初在细菌、真菌和植物中被鉴定出来，随后在原生生物和某些动物类群（包括海鞘）中被发现。编码NDH-2的基因也存在于一些环节动物、缓步动物和甲壳类动物的基因组中。二十多年来，NDH-2一直作为有缺陷的复合体I的潜在替代品进行研究。在模式生物中，NDH-2已被证明可以改善与复合体I功能障碍相关的广泛病症，包括帕金森病的症状。最近，在以异源方式表达NDH-2的动物中观察到了寿命延长。已经提出了多种NDH-2可能延长寿命的机制。这些机制包括通过调节NAD/NADH比值激活长寿途径、减少线粒体中活性氧（ROS）的产生，或者通过适度增加ROS的产生随后激活防御途径（线粒体应激）。本综述概述了关于NDH-2的最新研究，包括NDH-2的结构特点、其抑制剂、其在分枝杆菌和顶复门寄生虫致病性中的作用以及其在细菌、真菌和动物中的功能。
