2.5.3. NDUFB10

The gene for NDUFB10 is located on chromosome 16. The NDUFB10 protein has 172 amino acids and a mass of 20.8 kDa. It lacks a mitochondrial import sequence. It is one of four IMS proteins found in complex I, and all have four cysteine residues that form two disulfide bonds. In NDUFB10, two cysteine residues, Cys78 and Cys107, are found near the ends of a long alpha-helix (M77–E111). These cysteine residues form disulfides with nearby cysteines, connected to the long helix by loops of 6–11 residues. Cys78 forms its disulfide with Cys71, and Cys107 forms its disulfide with Cys119. In addition, there is

another cysteine, Cys145, conserved among vertebrates, and of unknown significance. The import of NDUFB10 is dependent upon its oxidation by CHCHD4/Mia40 and its formation of correct disulfide bonds [64]. NDUFB10 also contains three additional alpha-helices, two C-terminal ones and one N-terminal one. These extensions allow it to contact many subunits in the vicinity of ND4 and ND5. It primarily contacts NDUFB5, NDUFB6, and NDUFB11, with lesser contact to ND4, ND5, and NDUFC2. In an analysis of cultured cells, the knockout of NDUFB10 resulted in a loss of complex I assembly and, especially, the ND4/5 modules. ‐ ‐ ‐

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One individual with mutations in NDUFB10 was studied [64]. She was compound heterozygous with a paternally inherited termination codon at Glu70 of NDUFB10 and a maternally inherited p.Cys107Ser substitution. This infant presented with lactic acidosis and cardiomyopathy and survived for only about one day. An analysis revealed reduced levels of complex I activity, reduced levels of in-gel assays of complex I in BN gels, and the presence of the Cys107Ser protein in the cytosol. The transcript of the nonsense allele was not found by RT-PCR. Cys107 is not near any other subunits, the closest being NDUFB5, NDUFB6, and NDUFB11. Given the healthy status of the parents, it appears that the Cys107S mutant does not have a dominant negative phenotype. Rather, it primarily does not enter the mitochondrion, and if another allele is available, complex I can assemble without difficulty. ‐ ‐ *‐*
