Fig. 7. Proposed model of the mechanism of ACAD9-ECSIT assembly and its functional implications in FAO and OXPHOS pathways.

In absence of ECSIT, ACAD9 acts as an acyl-CoA dehydrogenase enzyme in the first step of the FAO pathway. Dehydrogenation of the acyl-CoA substrate is concomitant with the reduction of the FAD prosthetic group into FADH₂. Upon recognition of ACAD9 by ECSIT, the gatekeeper loop in ACAD9 flips upwards, allowing the concomitant binding of ECSIT and deflavination, shutting down the dehydrogenase activity of ACAD9 and becoming committed to CI assembly. ECSIT dephosphorylation would enable the binding to ACAD9 and hence, act as a potential trigger to favour the assembly of the MCIA complex.