Structures of Tetrahymena thermophila respiratory megacomplexes on the tubular mitochondrial cristae.

Tetrahymena thermophila, a classic ciliate model organism, has been shown to possess tubular mitochondrial cristae and highly divergent electron transport chain involving four transmembrane protein complexes (I-IV). Here we report cryo-EM structures of its ~8 MDa megacomplex IV 2  + (I + III 2  + II) 2 , as well as a ~ 10.6 MDa megacomplex (IV 2  + I + III 2  + II) 2 at lower resolution. In megacomplex IV 2  + (I + III 2  + II) 2 , each CIV 2 protomer associates one copy of supercomplex I + III 2 and one copy of CII, forming a half ring-shaped architecture that adapts to the membrane curvature of mitochondrial cristae. Megacomplex (IV 2  + I + III 2  + II) 2 defines the relative position between neighbouring half rings and maintains the proximity between CIV 2 and CIII 2 cytochrome c binding sites. Our findings expand the current understanding of divergence in eukaryotic electron transport chain organization and how it is related to mitochondrial morphology.