Proteomics

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The mitochondrial acyl-carrier protein interaction network highlights important roles for LYRM family members in complex I and mitoribosome assembly


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 many LYRM proteins have been well described in a variety of different 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 required for normal assembly of the large mitoribosome subunit, consistent with recent structural studies. In addition, we use 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 in conjunction with NDUFAB1.

INSTRUMENT(S): Orbitrap Fusion Lumos, LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: David Stroud  

LAB HEAD: David A Stroud

PROVIDER: PXD013706 | Pride | 2019-10-31

REPOSITORIES: Pride

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Publications

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

Dibley Marris G MG   Formosa Luke E LE   Lyu Baobei B   Reljic Boris B   McGann Dylan D   Muellner-Wong Linden L   Kraus Felix F   Sharpe Alice J AJ   Stroud David A DA   Ryan Michael T MT  

Molecular & cellular proteomics : MCP 20191030 1


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 know  ...[more]

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