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.