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线粒体酰基辅酶 A 载体蛋白(ACP)在代谢状态感知和线粒体功能的界面。

Mitochondrial acyl carrier protein (ACP) at the interface of metabolic state sensing and mitochondrial function.

机构信息

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

出版信息

Biochim Biophys Acta Mol Cell Res. 2019 Dec;1866(12):118540. doi: 10.1016/j.bbamcr.2019.118540. Epub 2019 Aug 29.

DOI:10.1016/j.bbamcr.2019.118540
PMID:31473256
Abstract

Acyl carrier protein (ACP) is a principal partner in the cytosolic and mitochondrial fatty acid synthesis (FAS) pathways. The active form holo-ACP serves as FAS platform, using its 4'-phosphopantetheine group to present covalently attached FAS intermediates to the enzymes responsible for the acyl chain elongation process. Mitochondrial unacylated holo-ACP is a component of mammalian mitoribosomes, and acylated ACP species participate as interaction partners in several ACP-LYRM (leucine-tyrosine-arginine motif)-protein heterodimers that act either as assembly factors or subunits of the electron transport chain and Fe-S cluster assembly complexes. Moreover, octanoyl-ACP provides the C8 backbone for endogenous lipoic acid synthesis. Accumulating evidence suggests that mtFAS-generated acyl-ACPs act as signaling molecules in an intramitochondrial metabolic state sensing circuit, coordinating mitochondrial acetyl-CoA levels with mitochondrial respiration, Fe-S cluster biogenesis and protein lipoylation.

摘要

酰基辅酶 A 蛋白 (ACP) 是细胞质和线粒体脂肪酸合成 (FAS) 途径中的主要合作伙伴。其活性形式全酶 ACP 作为 FAS 平台,利用其 4′-磷酸泛酰巯基乙胺基团将共价连接的 FAS 中间产物呈现给负责酰基链延伸过程的酶。线粒体未酰化的全酶 ACP 是哺乳动物线粒体核糖体的组成部分,并且酰化的 ACP 物种作为几种 ACP-LYRM(亮氨酸-酪氨酸-精氨酸基序)-蛋白异二聚体的相互作用伙伴参与,这些异二聚体要么作为组装因子,要么作为电子传递链和 Fe-S 簇组装复合物的亚基。此外,辛酰-ACP 为内源性硫辛酸合成提供 C8 骨架。越来越多的证据表明,mtFAS 生成的酰基辅酶 ACP 作为一种信号分子,在一种线粒体代谢状态感应回路中发挥作用,协调线粒体乙酰辅酶 A 水平与线粒体呼吸、Fe-S 簇生物发生和蛋白质硫辛酰化。

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