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Respiratory Complex III Is Required to Maintain Complex I in Mammalian Mitochondria

Respiratory Complex III Is Required to Maintain Complex I in Mammalian Mitochondria,10.1016/S1097-2765(04)00124-8,Molecular Cell,Rebeca Acı́n-Pérez,Ma

Respiratory Complex III Is Required to Maintain Complex I in Mammalian Mitochondria   (Citations: 60)
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A puzzling observation in patients with oxidative phosphorylation (OXPHOS) deficiencies is the presence of combined enzyme complex defects associated with a genetic alteration in only one protein-coding gene. In particular, mutations in the mtDNA encoded cytochrome b gene are associated either with combined complex I+III deficiency or with only complex III deficiency. We have reproduced the combined complex I+III defect in mouse and human cultured cell models harboring cytochrome b mutations. In both, complex III assembly is impeded and causes a severe reduction in the amount of complex I, not observed when complex III activity was pharmacologically inhibited. Metabolic labeling in mouse cells revealed that complex I was assembled, although its stability was severely hampered. Conversely, complex III stability was not influenced by the absence of complex I. This structural dependence among complexes I and III was confirmed in a muscle biopsy of a patient harboring a nonsense cytochrome b mutation.
Journal: Molecular Cell - MOL CELL , vol. 13, no. 6, pp. 805-815, 2004
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    • ...35 As shown in Figure 1a, the level of mitochondrial DNA was reduced to near background levels in EL4-&rho0 compared with EL4 cells, corroborating previous findings with other cell lines...

    Juan I Aguilóet al. Granzyme B of cytotoxic T cells induces extramitochondrial reactive ox...

    • ...The role of these supercomplexes is not clear but may involve substrate channeling, as well as complex stability (1, 17, 27)...
    • ...In addition, roles for apoptosis-inducing factor, complex III, and complex IV in complex I biogenesis have been identified (1, 7, 27, 36)...
    • ...Subunits CO1 (1), cytochrome b (2), CO3 (3), CO2 (4), ATP6 (5), and ATP8 (6) are indicated...
    • ...Indeed, complex III and, perhaps, complex IV may act as scaffolds to facilitate complex I assembly since loss of either has been found to lead to reduced complex I levels (1, 7)...

    Michael Lazarouet al. Analysis of the Assembly Profiles for Mitochondrial and Nuclear-DNA-En...

    • ...Two recent studies identified that complex I stability is reliant on an intact complex III [17,18], and this may relate to the association of these complexes within a supercomplex...

    Matthew McKenzieet al. Analysis of mitochondrial subunit assembly into respiratory chain comp...

    • ...Unexpectedly, the lack of Cox10 had a strong effect on the levels of complex I. Similarly, mammalian cells harboring mutations in the apocytochrome b gene that preclude the assembly of complex III have a greatly compromised complex I stability (1, 26)...
    • ...Our results with KCN inhibition, as well as published data on cells growing on antimycin A (1), argue against the scenario where OXPHOS function, at least in the short term, is necessary to stabilize the complexes...
    • ...Because previous (1, 26) data showed that complex I is unstable if not associated with complex III, it was possible that the disruption of this interaction could lead to the decrease in complex I. However, two pieces of evidence suggest this is not the case: (i) the ratio of I/III to I is not changed in the KO cells, even though both are markedly reduced, and (ii) pulse-chase experiments could not detect complex I formation, suggesting ...

    Francisca Diazet al. Cytochrome c Oxidase Is Required for the Assembly/Stability of Respira...

    • ...We show a decrease in the levels of complex I in the hybrid clones containing high levels of CyB-MT or COX1-MT mtDNA (Fig. 4A and C). Complex I stability has been shown to depend on the levels of complex III in various organisms, including bacteria (27) and mammalian cells (8,28,29)...
    • ...It was shown that the synthesis of complex I subunits and their assembly occurs normally in complex III mutant cells, but in the absence of complex III, complex I is rapidly degraded (28)...

    Marilena D'Aurelioet al. Respiratory chain supercomplexes set the threshold for respiration def...

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