Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1.
Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1.
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DOI：
10.1042/bj20120118
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Sack MN
中科院分区：
文献类型：
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作者：
Scott I;Webster BR;Li JH;Sack MN
SIRT 3通过电子传递链蛋白中赖氨酸残基的脱乙酰化来调节呼吸。线粒体蛋白乙酰化是否受反调节程序控制仍然是一个谜。在这里，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重要组成部分。我们发现GCN 5L 1/Bloc 1 s1对抗SIRT 3的乙酰化和呼吸作用。GCN 5L 1是一种富含蛋白质的蛋白质，与原核乙酰转移酶具有显著的同源性。GCN 5L 1的基因敲除使线粒体蛋白乙酰化钝化，并且其在完整线粒体中的重建恢复蛋白乙酰化。GCN 5L 1与SIRT 3呼吸链靶点相互作用并促进其乙酰化，并逆转SIRT 3对线粒体蛋白乙酰化、呼吸和生物能量学的整体影响。这些数据将GCN 5L 1鉴定为线粒体乙酰转移酶程序的关键原核生物衍生组分。
SIRT3 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. Here we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1/Bloc1s1 counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology to 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. These data identify GCN5L1 as a critical, prokaryote-derived component of the mitochondrial acetyltransferase program.