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

Zhou, Long; Maldonado, María; Padavannil, Abhilash; Guo, Fei; Letts, James A · Science · 2022

basic_science · Level V

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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-CIII<sub>2</sub> (Tt-SC I+III<sub>2</sub>) and a structure of Tt-CIV<sub>2</sub>. Tt-SC I+III<sub>2</sub> (~2.3 megadaltons) is a curved assembly with structural and functional symmetry breaking. Tt-CIV<sub>2</sub> is a ~2.7-megadalton dimer with more than 50 subunits per protomer, including mitochondrial carriers and a TIM8<sub>3</sub>-TIM13<sub>3</sub>-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.

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