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Sideroflexin 4 is a Complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module

ABSTRACT: Sideroflexins (SFXNs) comprise a family of five paralogous proteins (SFXN1-5) in metazoan species. SFXN1/2/3 function as serine transporters and are required for efficient mitochondrial one-carbon (1C) metabolism. SFXN4 is evolutionarily divergent and mutations in SFXN4 give rise to mitochondrial disease, pointing to a distinct function of this protein in mitochondrial biology. Using a combination of genome editing, interaction studies, and quantitative proteomics we show that loss of SFXN4 leads to an isolated complex I assembly defect and that SFXN4 interacts with the core components of the mitochondrial complex I intermediate assembly (MCIA) complex. Our findings suggest that SFXN4 is required for the incorporation of the mtDNA-encoded ND6 subunit in the ND2 assembly module of complex I. These findings provide new insights into the fundamental process of complex I assembly and functional insights into a disease-causing gene belonging to the sideroflexin family.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: David Stroud

LAB HEAD: David Stroud

PROVIDER: PXD032762 | Pride | 2022-03-23

REPOSITORIES: Pride

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