Structural organization of mitochondrial human complex I: role of the ND4 and ND5 mitochondria-encoded subunits and interaction with the prohibitin.
Bourges I, Ramus C, Mousson De Camaret B, Beugnot R, Remacle C, Cardol P, Hofhaus G, Issartel JP
Biochemical Journal (2004)
Category: respiration, complex I ¤ Added: Jul 19, 2004 ¤ Rating: ◊◊
Mitochondria-encoded NADH dehydrogenase (ND) subunits, as components of the hydrophobic part of complex I, are essential for NADH:ubiquinone oxidoreductase activity. Mutations or lack of expression of these subunits have dramatic pathogenic consequences in humans. However, the way these events affect complex I assembly is poorly documented. To understand the effects of particular mutations in ND subunits on complex I assembly, we studied four human cell lines: ND4 non expressing cells, ND5 non expressing cells, and rho o cells that do not express any ND subunits, in comparison to normal complex I control cells. In control cells, all of the 7 nuclear-encoded complex I subunits analyzed were found attached to the mitochondrial inner membrane, except the 24 kDa subunit, which was found nearly equally partitioned between the membranes and the matrix. Absence of only one, or even all seven ND subunits, did not cause major changes in the nuclear-encoded complex I subunit content of mitochondria. However, in cells lacking ND4 or ND5, very low amounts of 24 kDa were found associated with the membranes while most of the other nuclear-encoded subunits remained attached. In contrast, membrane association of most of the nuclear subunits was dramatically reduced in the absence of all seven ND proteins. Immunopurification detected several subcomplexes. One of these, containing the 23, 30 and 49 kDa subunits, also contained prohibitin. This is the first description of prohibitin interaction with complex I subunits and suggests that this protein might play a role in the assembly or degradation of mitochondrial complex I.