ABSTRACT

Mitochondrial dysfunction is involved in Alzheimer’s disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.

Area covered: Proteomics studies and their contribution to our understanding of mitochondrial dysfunction in AD pathogenesis.

Expert opinion: Proteomics has proven to be an efficient tool to uncover various aspects of this complex organelle, which will broaden our understanding of mitochondrial dysfunction in AD. Evidently, mitochondrial dysfunction is an early biochemical event that might play a central role in driving AD pathogenesis.

摘要

线粒体功能障碍与阿尔茨海默病 (AD) 发病机制有关。线粒体有自己的遗传物质；然而，它们的大部分蛋白质（~99%）在胞质核糖体上作为前体合成，然后输入线粒体。因此，探索这些细胞器中的蛋白质组变化可以产生有价值的信息，并阐明 AD 中线粒体功能障碍的分子机制。在这里，我们回顾了与 AD 相关的线粒体变化，包括β淀粉样蛋白和 tau 蛋白积累对线粒体蛋白质组的影响。我们还讨论了 ApoE 基因多态性与线粒体变化的关系，并对 AD 线粒体中各种差异表达蛋白进行了荟萃分析。

涵盖的领域：蛋白质组学研究及其对我们理解 AD 发病机制中线粒体功能障碍的贡献。

专家意见：蛋白质组学已被证明是揭示这种复杂细胞器各个方面的有效工具，这将拓宽我们对 AD 线粒体功能障碍的理解。显然，线粒体功能障碍是一种早期生化事件，可能在驱动 AD 发病机制中起核心作用。