Multifunctional Mitochondrial AAA Proteases.
Multifunctional Mitochondrial AAA Proteases.
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DOI：
10.3389/fmolb.2017.00034
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发表时间：
2017
影响因子：
5
通讯作者：
Glynn SE
中科院分区：
文献类型：
--
作者：
Glynn SE
线粒体执行真核细胞生存所必需的许多功能。这些活动是由一个不同的补充蛋白质编码的核和线粒体基因组，必须妥善组织和维护协调。线粒体蛋白质稳态的失调损害细胞器功能，并可能导致严重的人类疾病的发展。ATP驱动的AAA+蛋白通过根据细胞的需要去除和重塑蛋白质分子，在保护线粒体活性方面发挥着至关重要的作用。两种线粒体AAA蛋白酶i-AAA和m-AAA锚定在线粒体内膜的任一面，在那里它们接合并处理一系列底物以影响蛋白质生物合成、质量控制和关键代谢途径的调节。这些蛋白酶的功能通过多种底物依赖性作用模式扩展，包括完全降解、部分加工或在没有蛋白水解的情况下从膜上移位。这篇综述讨论了最近的进展，阐明基板的识别，处理和降解，使这些多功能的蛋白酶控制不同的活动，在这个多功能的细胞器的机制。
Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.