Supernumerary subunits NDUFA3, NDUFA5 and NDUFA12 are required for the formation of the extramembrane arm of human mitochondrial complex I.
Mammalian complex I is composed of fourteen highly conserved core subunits and additional thirty subunits acquired in the course of evolution. At present, the function of the majority of these supernumerary subunits is poorly understood. In this work, we have studied NDUFA3, NDUFA5 and NDUFA12 supernumerary subunits to gain insight into their role in CI activity and biogenesis. Using human cell lines in which the expression of these subunits was knocked down with miRNAs, we showed that they are necessary for the formation of a functional holoenzyme. Analysis of the assembly intermediates in mitochondria depleted for these subunits further suggested that they are required for assembly and/or stability of the electron transferring Q module in the peripheral arm of the CI.
INSERM UMR 1141, Bâtiment Ecran, Hôpital Robert Debré, 48 Boulevard Serurier, 75019 Paris, France. Electronic address: Malgorzata.rak@inserm.fr.
Malgorzata
M
Rak
INSERM UMR 1141, Bâtiment Ecran, Hôpital Robert Debré, 48 Boulevard Serurier, 75019 Paris, France.
Pierre
P
Rustin
D042967:Electron Transport Complex I / Q000378:metabolism*; D004795:Enzyme Stability; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference
C000589145:NDUFA12 protein, human; C510270:NDUFA3 protein, human; C508060:NDUFA5 protein, human; D021122:Protein Subunits; D009252:NADPH Dehydrogenase; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I
Mitochondria; Mitochondrial complex I; NADH ubiquinone oxidoreductase; Respiratory chain; Supernumerary CI subunit