ACP Acylation Is an Acetyl-CoA-Dependent Modification Required for Electron Transport Chain Assembly

• Published in: Molecular cell 2018-08, Vol.71 (4), p.567-580.e4
• Main Authors: Van Vranken, Jonathan G., Nowinski, Sara M., Clowers, Katie J., Jeong, Mi-Young, Ouyang, Yeyun, Berg, Jordan A., Gygi, Jeremy P., Gygi, Steven P., Winge, Dennis R., Rutter, Jared
• Format: Article
• Language: English
• Subjects: Acetyl Coenzyme A - metabolism; acetyl-CoA; Acyl Carrier Protein - chemistry; Acyl Carrier Protein - genetics; Acyl Carrier Protein - metabolism; Acylation; Allosteric Regulation; assembly factors; Binding Sites; Citric Acid Cycle - genetics; Electron Transport - genetics; electron transport chain; Fatty Acids - biosynthesis; Gene Expression Regulation, Fungal; mitochondria; Mitochondria - enzymology; Mitochondria - genetics; mitochondrial fatty acid synthesis; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Models, Molecular; Oxidation-Reduction; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Processing, Post-Translational; respiration; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2018.06.039

The electron transport chain (ETC) is an important participant in cellular energy conversion, but its biogenesis presents the cell with numerous challenges. To address these complexities, the cell utilizes ETC assembly factors, which include the LYR protein family. Each member of this family interacts with the mitochondrial acyl carrier protein (ACP), the scaffold protein upon which the mitochondrial fatty acid synthesis (mtFAS) pathway builds fatty acyl chains from acetyl-CoA. We demonstrate that the acylated form of ACP is an acetyl-CoA-dependent allosteric activator of the LYR protein family used to stimulate ETC biogenesis. By tuning ETC assembly to the abundance of acetyl-CoA, which is the major fuel of the TCA cycle and ETC, this system could provide an elegant mechanism for coordinating the assembly of ETC complexes with one another and with substrate availability. [Display omitted] •Acyl-ACP is an allosteric activator of LYR motif-containing ETC assembly factors•ACP acylation is sensitive to perturbations in mitochondrial acetyl-CoA synthesis•ACP and mtFAS coordinate the activation of mitochondrial respiration We demonstrate that mitochondrial fatty acid synthesis (mtFAS) generates an acylated form of the acyl carrier protein (acyl-ACP), which is an allosteric activator of members of the LYR protein family. Acyl-ACP interacts with each member of the family to coordinately activate mitochondrial respiration, primarily through promoting electron transport chain assembly.