The Mitochondrial Acyl-carrier Protein Interaction Network Highlights Important Roles for LYRM Family Members in Complex I and Mitoribosome Assembly

Marris G. Dibley, Luke E. Formosa, Baobei Lyu, Boris Reljic, Dylan McGann, Linden Muellner-Wong, Felix Kraus, Alice J. Sharpe, David A. Stroud, Michael T. Ryan

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

NDUFAB1 is the mitochondrial acyl carrier protein (ACP) essential for cell viability. Through its pantetheine-4'-phosphate post-translational modification, NDUFAB1 interacts with members of the leucine-tyrosine-arginine motif (LYRM) protein family. Although several LYRM proteins have been described to participate in a variety of defined processes, the functions of others remain either partially or entirely unknown. We profiled the interaction network of NDUFAB1 to reveal associations with 9 known LYRM proteins as well as more than 20 other proteins involved in mitochondrial respiratory chain complex and mitochondrial ribosome assembly. Subsequent knockout and interaction network studies in human cells revealed the LYRM member AltMiD51 to be important for optimal assembly of the large mitoribosome subunit, consistent with recent structural studies. In addition, we used proteomics coupled with topographical heat-mapping to reveal that knockout of LYRM2 impairs assembly of the NADH-dehydrogenase module of complex I, leading to defects in cellular respiration. Together, this work adds to the catalogue of functions executed by LYRM family of proteins in building mitochondrial complexes and emphasizes the common and essential role of NDUFAB1 as a protagonist in mitochondrial metabolism.

Original languageEnglish
Pages (from-to)65-77
Number of pages13
JournalMolecular & Cellular Proteomics
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • acyl-carrier protein
  • affinity proteomics
  • blue native polyacrylamide gel electrophoresis
  • complex I
  • Mitochondria function or biology
  • protein complex analysis
  • protein structure
  • protein-protein interactions

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