Acyl modification and binding of mitochondrial ACP to multiprotein complexes

Heike Angerer1, Stefan Schönborn2, Jan Gorka2

  • 1Goethe University Frankfurt, Medical School, Institute of Biochemistry II, Structural Bioenergetics Group, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.

Insights

Mitochondrial acyl carrier proteins (ACPMs) are crucial for fatty acid synthesis and complex I function. Their interaction with LYR motif proteins is vital for complex assembly and stability.

Area of Science:

  • Mitochondrial biology
  • Protein biochemistry
  • Enzyme complex assembly

Background:

  • Mitochondrial acyl carrier protein (ACPM/NDUFAB1) is key to fatty acid synthesis type II.
  • ACPM's role as a respiratory complex I subunit was previously unclear.
  • Yarrowia lipolytica's Complex I has two ACPMs (ACPM1, ACPM2) linked by LYRM subunits.

Purpose of the Study:

  • Investigate the function and interactions of ACPMs in yeast Complex I.
  • Elucidate the role of ACPM-LYRM interactions in complex assembly and activity.
  • Determine the structural basis for ACPM-LYRM association.

Main Methods:

  • Protein complex isolation and characterization.
  • Yeast genetics and molecular biology techniques.
  • Biochemical assays for complex I activity and assembly.

Main Results:

  • ACPM1 exists both bound to Complex I and as a free protein.
  • ACPM1 also forms complexes with LYRM4(ISD11)/NFS1 involved in Fe-S cluster biogenesis.
  • A long acyl chain on the phosphopantetheine cofactor is essential for ACPM docking to protein complexes.
  • A novel protein-protein interaction motif mediating ACPM-LYRM association is proposed.

Conclusions:

  • ACPMs have multifaceted roles beyond fatty acid synthesis, including Complex I assembly and Fe-S cluster biogenesis.
  • Specific ACPM-LYRM interactions are critical for Complex I function and stability.
  • A conserved interaction motif likely governs ACPM-LYRM binding across different protein complexes.

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