ATAD3A：线粒体相关疾病的关键调节因子,International Journal of Molecular Sciences

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ATAD3A：线粒体相关疾病的关键调节因子
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2023-08-07 , DOI: 10.3390/ijms241512511
Liting Chen ₁ , Yuchang Li ₁ , Alexander Zambidis ₁ , Vassilios Papadopoulos ₁

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线粒体膜蛋白 ATAD3A 是含有 AAA 结构域的 ATP 酶超家族的成员。它对于维持线粒体 DNA、结构和功能非常重要。近年来，在出现神经系统症状的患者中发现了越来越多的 ATAD3A 突变。其中许多突变会破坏线粒体的结构、功能和动力学，对年轻患者来说是致命的。在此，我们总结了目前对ATAD3A与线粒体关系的认识，包括ATAD3A与线粒体DNA和线粒体/ER蛋白的相互作用、ATAD3A在胆固醇线粒体运输中的调节以及已知ATAD3A突变对线粒体功能的影响。在当前的综述中，我们揭示了 ATAD3A 的寡聚化以及与其他线粒体/ER 蛋白的相互作用对其各种功能至关重要。尽管影响蛋白质的不同结构域，但几乎所有在 ATAD3A 中观察到的记录突变都表现出功能丧失或显性失活效应，可能导致 ATAD3A 二聚化的破坏；自噬；线粒体自噬；线粒体数量、大小和嵴形态的改变；线粒体呼吸链复合物 I、IV 和 V 的活性降低。这些发现表明 ATAD3A 在线粒体动力学中发挥着关键作用，而线粒体动力学很容易受到 ATAD3A 突变变异的干扰。

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ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

Mitochondrial membrane protein ATAD3A is a member of the AAA-domain-containing ATPases superfamily. It is important for the maintenance of mitochondrial DNA, structure, and function. In recent years, an increasing number of ATAD3A mutations have been identified in patients with neurological symptoms. Many of these mutations disrupt mitochondrial structure, function, and dynamics and are lethal to patients at a young age. Here, we summarize the current understanding of the relationship between ATAD3A and mitochondria, including the interaction of ATAD3A with mitochondrial DNA and mitochondrial/ER proteins, the regulation of ATAD3A in cholesterol mitochondrial trafficking, and the effect of known ATAD3A mutations on mitochondrial function. In the current review, we revealed that the oligomerization and interaction of ATAD3A with other mitochondrial/ER proteins are vital for its various functions. Despite affecting different domains of the protein, nearly all documented mutations observed in ATAD3A exhibit either loss-of-function or dominant-negative effects, potentially leading to disruption in the dimerization of ATAD3A; autophagy; mitophagy; alteration in mitochondrial number, size, and cristae morphology; and diminished activity of mitochondrial respiratory chain complexes I, IV, and V. These findings imply that ATAD3A plays a critical role in mitochondrial dynamics, which can be readily perturbed by ATAD3A mutation variants.

更新日期：2023-08-07

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