(B) Structural reorganization of SCs in the absence of CIV. In control cells (top), subunits COX4 and COX5A form an independent subcomplex that binds newly-synthesized COX1, allowing the completion of CIV assembly and its further integration into respirasomes through canonical pathways. In COX1∆ cybrids (middle), SC I+III2 is rapidly degraded due to the absence of stabilizing CIV components. In COX2∆ cybrids (bottom), SC I+III2 is stabilized by the binding of a 'non-canonical' stable COX1-submodule (comprising subunits COX1, COX5B, COX7A2 and the assembly factor HIGD2A), likely by keeping this SC in an assembly-competent state for the further incorporation of CIV subunits/modules up to completion of respirasome biogenesis. 