鉴定线粒体乙酰转移酶程序的分子成分：GCN5L1 的新作用。
Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1.
机构信息
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1454, USA.
出版信息
Biochem J. 2012 May 1;443(3):655-61. doi: 10.1042/BJ20120118.
SIRT3 (sirtuin 3) modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondrial protein acetylation is controlled by a counter-regulatory program has remained elusive. In the present study we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1 [GCN5 (general control of amino acid synthesis 5)-like 1; also known as Bloc1s1] counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology with a prokaryotic acetyltransferase. Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics. The results of the present study identify GCN5L1 as a critical prokaryote-derived component of the mitochondrial acetyltransferase programme.
SIRT3（沉默信息调节因子 3）通过去乙酰化电子传递链蛋白中的赖氨酸残基来调节呼吸作用。线粒体蛋白乙酰化是否受反向调节程序控制一直难以捉摸。在本研究中，我们确定了这个以前未定义的线粒体乙酰转移酶系统的一个必需组成部分。我们表明，GCN5L1[GCN5（一般氨基酸合成的通用控制 5）样 1；也称为 Bloc1s1]可拮抗 SIRT3 的乙酰化和呼吸作用。GCN5L1 富含线粒体，并与原核乙酰转移酶具有显著同源性。GCN5L1 的基因敲低会削弱线粒体蛋白的乙酰化，而其在完整线粒体中的重新构建可恢复蛋白的乙酰化。GCN5L1 与 SIRT3 呼吸链靶标相互作用并促进其乙酰化，并逆转 SIRT3 对线粒体蛋白乙酰化、呼吸作用和生物能量学的全局影响。本研究的结果确定 GCN5L1 为线粒体乙酰转移酶系统中关键的原核衍生组成部分。
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