Bi-allelic UQCC1 variants impair mitochondrial complex III assembly causing early-onset mitochondrial disease

UQCC1

Biallelic variants in UQCC1, a complex III assembly factor: reduced UQCC1 and UQCC2 protein levels, impaired assembly of complex III and respiratory supercomplexes

UQCC1 encodes an assembly factor for complex III (CIII2) of the mitochondrial respiratory chain and had not previously been linked to human disease. The authors describe nine subjects from eight unrelated families carrying biallelic UQCC1 variants, with heterogeneous early-onset mitochondrial disease and lactic acidosis. In patient fibroblasts, levels of UQCC1 protein and its partner UQCC2 were reduced; BN-PAGE, quantitative proteomics and mass spectrometry complexome profiling showed decreased CIII2, impaired respiratory supercomplex formation and delayed incorporation of newly synthesised subunits. Lentiviral transduction of patient fibroblasts restored UQCC1 protein and CIII2 activity.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A preprint not yet peer reviewed, but the body of evidence is solid for a new gene: eight independent families, several convergent biochemical approaches and functional rescue in fibroblasts. For exome/genome interpretation, UQCC1 now belongs in the differential of early lactic acidosis with complex III deficiency. The abstract details neither phenotypes nor variants, which for now limits any genotype-phenotype correlation.

Analysis by Dr Thibaut Benquey