Abstract：
The malate aspartate shuttle (MAS) plays a pivotal role in transporting cytosolic reducing equivalents - electrons - into the mitochondria for energy conversion at the electron transport chain (ETC) and in the process of oxidative phosphorylation. The MAS consists of two pairs of cytosolic and mitochondrial isoenzymes (malate dehydrogenases 1 and 2; and glutamate oxaloacetate transaminases 1 and 2) and two transporters (malate-2-oxoglutarate carrier and aspartate glutamate carrier (AGC), the latter of which has two tissue-dependent isoforms AGC1 and AGC2). While the inner mitochondrial membrane is impermeable to NADH, the MAS forms one of the main routes for mitochondrial electron uptake by promoting uptake of malate. Inherited bi-allelic pathogenic variants in five of the seven components of the MAS have been described hitherto and cause a wide spectrum of symptoms including early-onset epileptic encephalopathy. This review provides an overview of reported patients suffering from MAS deficiencies. In addition, we give an overview of diagnostic procedures and research performed on patient-derived cellular models and tissues. Current cellular models are briefly discussed and novel ways to achieve a better understanding of MAS deficiencies are highlighted.
摘要：
苹果酸天冬氨酸穿梭（MAS）在将胞质还原当量-电子-运输到线粒体中进行电子运输链（ETC）的能量转换以及氧化磷酸化过程中起着关键作用。MAS由两对细胞溶质和线粒体同工酶（苹果酸脱氢酶1和2；谷氨酸草酰乙酸转氨酶1和2）和两个转运蛋白（苹果酸-2-氧戊二酸载体和天冬氨酸谷氨酸载体（AGC）组成，后者具有两个组织依赖性同工型AGC1和AGC2)。虽然线粒体内膜对NADH是不可渗透的，MAS通过促进苹果酸的摄取形成线粒体电子摄取的主要途径之一。迄今为止，已经描述了MAS的七个组成部分中的五个中的遗传双等位基因致病变体，并引起广泛的症状，包括早发性癫痫性脑病。这篇综述概述了已报道的MAS缺陷患者。此外,我们概述了在患者来源的细胞模型和组织上进行的诊断程序和研究.简要讨论了当前的细胞模型，并强调了更好地理解MAS缺陷的新方法。
