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Abstract
Complex I (CI) is the largest enzyme of the mammalian mitochondrial respiratory chain. The biogenesis of the complex is a very complex process due to its large size and number of subunits (45 subunits). The situation is further complicated due to the fact that its subunits have a double genomic origin, as seven of them are encoded by the mitochondrial DNA. Understanding of the assembly process and characterization of the involved factors has advanced very much in the last years. However, until now, a key part of the process, that is, how and at which step the mitochondrially encoded CI subunits (ND subunits) are incorporated in the CI assembly process, was not known. Analyses of several mouse cell lines mutated for three ND subunits allowed us to determine the importance of each one for complex assembly/stability and that there are five different steps within the assembly pathway in which some mitochondrially encoded CI subunit is incorporated.
Supplemental material for this article may be found at http://mcb.asm.org/.
We are very grateful to Leo G. J. Nijtmans and Rutger O. Vogel for critically reading the manuscript. We thank Santiago Morales for his technical assistance.
Our work was supported by the Spanish Ministry of Science (SAF2009-08007 and CSD2007-00020), the EU (EUMITOCOMBAT-LSHM-CT-2004-503116), a Marie Curie European Reintegration Grant (PERG04-GA-2008-239372), and Group of Excellence grant DGA (B55). E.P.-C. was supported by an FPI fellowship, E.F.-V. by a Juan de la Cierva postdoctoral grant, and M.P.B.-B. by a Ramon y Cajal postdoctoral grant, all three provided by the Spanish MICINN.