This article presents a personal and critical review of the history of the malate–aspartate shuttle (MAS), starting in 1962 and ending in 2020. The MAS was initially proposed as a route for the oxidation of cytosolic NADH by the mitochondria in Ehrlich ascites cell tumor lacking other routes, and to explain the need for a mitochondrial aspartate aminotransferase (glutamate oxaloacetate transaminase 2 [GOT2]). The MAS was soon adopted in the field as a major pathway for NADH oxidation in mammalian tissues, such as liver and heart, even though the energetics of the MAS remained a mystery. Only in the 1970s, LaNoue and coworkers discovered that the efflux of aspartate from mitochondria, an essential step in the MAS, is dependent on the proton‐motive force generated by the respiratory chain: for every aspartate effluxed, mitochondria take up one glutamate and one proton. This makes the MAS in practice uni‐directional toward oxidation of cytosolic NADH, and explains why the free NADH/NAD ratio is much higher in the mitochondria than in the cytosol. The MAS is still a very active field of research. Most recently, the focus has been on the role of the MAS in tumors, on cells with defects in mitochondria and on inborn errors in the MAS. The year 2019 saw the discovery of two new inborn errors in the MAS, deficiencies in malate dehydrogenase 1 and in aspartate transaminase 2 (GOT2). This illustrates the vitality of ongoing MAS research.

中文翻译：

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苹果酸-天冬氨酸穿梭（博斯特循环）：它是如何开始并发展成为主要代谢途径的


本文对从 1962 年开始到 2020 年结束的苹果酸-天冬氨酸穿梭机 (MAS) 的历史进行了个人和批判性的回顾。MAS 最初被提出作为艾利希腹水细胞中线粒体氧化胞质 NADH 的途径肿瘤缺乏其他途径，并解释对线粒体天冬氨酸转氨酶（谷氨酸草酰乙酸转氨酶 2 [GOT2]）的需要。尽管 MAS 的能量学仍然是个谜，但 MAS 很快就被该领域采用，作为哺乳动物组织（如肝脏和心脏）中 NADH 氧化的主要途径。直到 20 世纪 70 年代，LaNoue 和同事才发现，天冬氨酸从线粒体流出（MAS 中的一个重要步骤）依赖于呼吸链产生的质子动力：每流出一个天冬氨酸，线粒体就会吸收一个谷氨酸和一个谷氨酸。质子。这使得 MAS 实际上单向氧化细胞质 NADH，并解释了为什么线粒体中的游离 NADH/NAD 比率比细胞质中的高得多。 MAS 仍然是一个非常活跃的研究领域。最近，人们关注的焦点是 MAS 在肿瘤中的作用、线粒体缺陷的细胞以及 MAS 的先天性缺陷。 2019 年，MAS 中发现了两种新的先天性缺陷，即苹果酸脱氢酶 1 和天冬氨酸转氨酶 2 (GOT2) 缺陷。这说明了正在进行的 MAS 研究的活力。