Cardiology Division, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
Trends Cell Biol. 2018 May;28(5):346-355. doi: 10.1016/j.tcb.2018.01.007. Epub 2018 Feb 21.
General control of amino acid synthesis 5 (GCN5) like-1 (GCN5L1) was identified as a novel gene with sequence homology to the histone acetyltransferase Gcn5. Subsequent protein-interaction studies identified GCN5L1 as a subunit of the multiprotein lysosome biogenesis complex, resulting in an alternative designation as biogenesis of lysosome-related organelle complex 1 subunit 1 (BLOS1 or BLOC1S1). Despite the distinct nomenclatures, GCN5L1/BLOS1 has been shown to play crucial roles in mitochondria, endosomes, lysosomes, and synaptic vesicle precursors (SVPs). GCN5L1/BLOS1 controls mitochondrial protein acetylation, modulates metabolic pathways, and orchestrates retrograde mitochondria-to-nucleus signaling. It also contributes to endosome-lysosome and vesicle trafficking and to endolysosomal function. Here we discuss the intracellular roles of GCN5L1/BLOS1 in the hope of linking mitochondria-centric effects to cytosolic vesicle biology.
氨基酸合成 5（GCN5）样 1（GCN5L1）的一般调控被鉴定为一种具有与组蛋白乙酰转移酶 Gcn5 序列同源性的新型基因。随后的蛋白质相互作用研究将 GCN5L1 鉴定为多蛋白溶酶体生物发生复合物的一个亚基，导致其被赋予另一个名称为溶酶体相关细胞器生物发生复合物 1 亚基 1（BLOS1 或 BLOC1S1）。尽管存在不同的命名法，但 GCN5L1/BLOS1 已被证明在线粒体、内体、溶酶体和突触小泡前体（SVPs）中发挥关键作用。GCN5L1/BLOS1 控制线粒体蛋白乙酰化，调节代谢途径，并协调逆行线粒体到细胞核信号。它还有助于内体-溶酶体和囊泡运输以及内溶酶体功能。在这里，我们讨论了 GCN5L1/BLOS1 在细胞内的作用，希望将以线粒体为中心的效应与细胞质囊泡生物学联系起来。
