Structures of <i>Tetrahymena</i> ’s respiratory chain reveal the diversity of eukaryotic core metabolism

Abstract

Respiration is a core biological energy-converting process whose last steps are carried out by a chain of multisubunit complexes in the inner mitochondrial membrane. To probe the functional and structural diversity of eukaryotic respiration, we examined the respiratory chain of the ciliate <i>Tetrahymena thermophila</i> (Tt). Using cryo-electron microscopy on a mixed sample, we solved structures of a supercomplex between Tt complex I (Tt-CI) and Tt-CIII₂ (Tt-SC I+III₂) and a structure of Tt-CIV₂. Tt-SC I+III₂ (~2.3 megadaltons) is a curved assembly with structural and functional symmetry breaking. Tt-CIV₂ is a ~2.7-megadalton dimer with more than 50 subunits per protomer, including mitochondrial carriers and a TIM8₃-TIM13₃-like domain. Our structural and functional study of the <i>T. thermophila</i> respiratory chain reveals divergence in key components of eukaryotic respiration, thereby expanding our understanding of core metabolism.