SC consist of various ratios of copies of individual complexes (I, III, IV, and V) to form stable, supramolecular structures; for instance, CI forms a supercomplex with [CIII.sub.2] and CIV (known as the respirasome), as well as with [CIII.sub.2] alone (SC I + [III.sub.2]).
Winge, "Sealing the mitochondrial respirasome," Molecular and Cellular Biology, vol.
Milenkovic et al., "COX7A2L is a mitochondrial complex III binding protein that stabilizes the [III.sub.2] + IV supercomplex without affecting respirasome formation," Cell Reports, vol.
Boekema, "Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography," Proceedings of the National Academy of Sciences of the United States of America, vol.
Garcia-Consuegra et al., "Mitochondrial complex I plays an essential role in human respirasome assembly," Cell Metabolism, vol.
The RC complex I is considered to be the most important component in these assemblies, and it is a member of almost all known respirasomes [70-74].
Among the various types of association, the I + [III.sub.2] + [IV.sub.1-4] supercomplex or the respirasome
is one of the most intriguing supercomplexes, because it considered the minimal unit to perform complete respiration from NADH to oxygen [29, 31].
Milenkovic et al., "COX7A2L is a mitochondrial complex III binding protein that stabilizes the III2+IV supercomplex without affecting respirasome
formation," Cell Reports, vol.
III is associated with complexes I and IV to form the respirasome. UQCC2 is required for complex III assembly.
The majority of complex I is found bound with a complex III dimer and complex IV (CI, [CIII.sub.2], and CIV) termed respirasome or with a complex III dimer alone (CI, [CIII.sub.2]).
Taken together, these results indicate that CYC1 mutations might cause a defect in respirasome assembly and a combined OXPHOS deficiency.