Figure 3.

Roles of HIGD1A and HIGD2A in cytochrome c oxidase assembly. (a) Schematic view of the mammalian modular cytochrome c oxidase assembly pathway. HIGD1A is present in an early assembly cluster, together with the COX1 module proteins COX4-1 and COX5A. HIGD2A forms a 50 kDa regulatory module with COX4-1, COX5B, and COX6A1, which binds to newly synthesized COX3 to promote its binding to the previously assembled COX1 + COX2 module. HIGD1A and HIGD2A are represented by a blue and a green box, respectively, due to the lack of structural information. (b) The HIGD2A regulatory module plays a role in supercomplexed cytochrome c oxidase assembly, by interacting with SC I+III₂ and facilitating the incorporation of the remaining CIV subunits. The figure was generated with PyMOL and Adobe Photoshop using the structure of the CI-CIII₂-CIV respirasome from ovine heart mitochondria [81] (PDB 5J4Z). IMS: intermembrane space. IMM: inner mitochondrial membrane. CI: complex I. CIII₂: complex III dimer. CIV: complex IV.