Fig. 2: The lumenal III₂–IV interface generates an apicomplexan-specific supercomplex architecture that reflects cristae morphology.

a, A slice of an electron cryo-tomogram of mitochondrial membranes from T. gondii. ATP synthase (yellow) and supercomplexes (red) are indicated. b, The subtomogram average map (gray) is consistent with a III₂–IV₁ arrangement. The individually fitted CIII dimer (blue) and CIV monomer structures (yellow) are from S. cerevisiae (PDB 6T15). c, A three-dimensional close-up of a showing apical ATP synthase and lateral supercomplex. The apices of the mitochondrial membranes (blue) are occupied by ATP synthase pyramids (yellow, described in ref. ¹³), with supercomplexes (red) in the flatter lateral regions. Both structures were obtained by subtomogram averaging. d, The arrangement of ATP synthase and supercomplexes in cristae of mammals and T. gondii. The rim of flat cristae in mammals are in line with ATP synthase rows (PDB 7ajb), whereas the apices of bulbous T. gondii cristae are shaped by ATP synthase pyramids (PDB 6TML). Mammalian supercomplexes (PDB 7o37) are found in the lateral, flat membrane regions, whereas the kinked III₂–IV T. gondii supercomplex (this study) is accommodated by the curved, lateral regions. The matrix is shown in yellow. The cristae lumen and intermembrane space are shown in blue. e, A schematic highlighting the resulting cristae morphologies, adapted from ref. ⁴³. f, Overlay of supercomplex structures aligned on CIV highlights different architectures, as revealed by differing positions of CIII from mammals (Mus musculus, PDB 7o37 mature supercomplex), yeast (S. cerevisiae, PDB 6giq) and plant (Vigna radiata, PDB 7jrp). The mammalian and T. gondii CIII homologs bind to opposite sides of CIV. g, Comparison of the T. gondii (this study) and M. musculus III₂–IV (PDB 7o37) showing the rotation of CIV relative to CIII, thereby placing different CIV subunits (COX6B and COX7c) at the interface with QCR6, or at the distal end of the supercomplex. h, Open-book view of the III₂–IV interface with lumenal contacts with respective subunits highlighted by spheres. i, Top view of the III₂–IV interface.