Dissecting the concordant and disparate roles of NDUFAF3 and NDUFAF4 in mitochondrial complex I biogenesis.

ABSTRACT: Distinct sub-assemblies (modules) of mitochondrial complex I (CI) are assembled with the assistance of CI Assembly Factors (CIAFs) through mechanisms that are incompletely defined. Here, using genetic analyses in Drosophila, we report that when either of the CIAFs - NDUFAF3 or NDUFAF4 - is disrupted, biogenesis of the Q-, N-, and P_P-b-modules of CI is impaired. This is due, at least in part, to the compromised integration of NDUFS3 and NDUFS5 into the Q-, and P_P-b-modules, respectively, coupled with a destabilization of another CIAF, TIMMDC1, in assembly intermediates. Notably, forced expression of NDUFAF4 rescues the biogenesis defects in the Q-module and some aspects of the defects in the P_P-b-module of CI when NDUFAF3 is disrupted. Altogether, our

SUBMITTER: Murari A 

PROVIDER: S-EPMC8346666 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature