A Role for Human N-alpha Acetyltransferase 30 (Naa30) in Maintaining Mitochondrial Integrity
A Role for Human N-alpha Acetyltransferase 30 (Naa30) in Maintaining Mitochondrial Integrity
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DOI：
10.1074/mcp.m116.061010
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发表时间：
2016-11-01
影响因子：
7
通讯作者：
Arnesen, Thomas
中科院分区：
文献类型：
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作者：
Van Damme, Petra;Kalvik, Thomas V.;Arnesen, Thomas
N-末端乙酰基转移酶（N-terminal acetyltransferases，NAT）引起的N-末端乙酰化（N-terminal acetylation，NT-acetylation）是真核生物中最常见的蛋白质修饰之一。NatC复合物代表了三种主要NAT之一，其中底物概况在很大程度上尚未探索。在这里，我们定义了在体内的人类NatC NT-乙酰基组的蛋白质组范围内结合敲除其催化亚基Naa 30与位置蛋白质组学。我们鉴定了46种人NatC底物，扩展了我们目前对NatC底物库的了解，现在包括含有Met-Leu、Met-Ile、Met-Phe、Met-Trp、Met-Val、Met-Met、Met-His和Met-Lys N末端的蛋白质。Naa 30耗竭后，发现几种细胞器蛋白的表达水平降低，特别是线粒体蛋白，其中一些被发现是NatC底物。有趣的是，Naa 30的敲低诱导线粒体膜电位的损失和线粒体片段化。总之，NatC N-乙酰化了大量的蛋白质，是线粒体的完整性和功能所必需的。
N-terminal acetylation (Nt-acetylation) by N-terminal acetyltransferases (NATs) is one of the most common protein modifications in eukaryotes. The NatC complex represents one of three major NATs of which the substrate profile remains largely unexplored. Here, we defined the in vivo human NatC Nt-acetylome on a proteome-wide scale by combining knockdown of its catalytic subunit Naa30 with positional proteomics. We identified 46 human NatC substrates, expanding our current knowledge on the substrate repertoire of NatC which now includes proteins harboring Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Val, Met-Met, Met-His and Met-Lys N termini. Upon Naa30 depletion the expression levels of several organellar proteins were found reduced, in particular mitochondrial proteins, some of which were found to be NatC substrates. Interestingly, knockdown of Naa30 induced the loss of mitochondrial membrane potential and fragmentation of mitochondria. In conclusion, NatC N-tacetylates a large variety of proteins and is essential for mitochondrial integrity and function.