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

Mol Cell. 2018 Aug 16;71(4):567-580.e4. doi: 10.1016/j.molcel.2018.06.039.

Abstract

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.

Keywords: acetyl-CoA; assembly factors; electron transport chain; mitochondria; mitochondrial fatty acid synthesis; respiration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / metabolism*
  • Acyl Carrier Protein / chemistry
  • Acyl Carrier Protein / genetics
  • Acyl Carrier Protein / metabolism*
  • Acylation
  • Allosteric Regulation
  • Binding Sites
  • Citric Acid Cycle / genetics
  • Electron Transport / genetics
  • Fatty Acids / biosynthesis
  • Gene Expression Regulation, Fungal
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • 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*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Acyl Carrier Protein
  • Fatty Acids
  • Fmc1 protein, S cerevisiae
  • Isd11 protein, S cerevisiae
  • Mitochondrial Proteins
  • Protein Isoforms
  • Saccharomyces cerevisiae Proteins
  • Acetyl Coenzyme A