Preprint / Version 1

How respiratory complexes and ATP synthase co-assemble to build cristae

This article is a preprint and has not been certified by peer review.

Authors

    Mengchen Wu,  
    Mengchen Wu
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
    Zhongqiu Li,  
    Zhongqiu Li
    • National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Shanghai, China.
    Zhuru Hou,  
    Zhuru Hou
    • Department of Microbiology and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Hongtao Tian,  
    Hongtao Tian
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Ruizhe Zhang,  
    Ruizhe Zhang
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Fangzhu Han,  
    Fangzhu Han
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Yiqi Hu,  
    Yiqi Hu
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Jiancang Zhou,  
    Jiancang Zhou
    • Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Shizhu Li,  
    Shizhu Li
    • National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Shanghai, China.
    Alexey Amunts,  
    Alexey Amunts
    • University of Münster, Schlossplatz 8, Münster, Germany
    • Institute of Bio-Architecture and Bio-Interactions, Shenzhen Medical Academy of Research and Translation, Shenzhen, Guangdong, China.
    Yue Liu,  
    Yue Liu
    • Department of Microbiology and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
    Long Zhou
    Long Zhou
    • Department of Biophysics and Department of Critical Care Medicine of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Categories
Molecular Biology
Keywords
cristae; oxidative phosphorylation; supercomplex; kinetoplastid; cryo-EM; cryo-ET

Abstract

Mitochondrial oxidative phosphorylation (OXPHOS) is often organized into spatially segregated domains, with ATP synthase (complex V, CV) oligomers shaping highly curved cristae rims and respiratory chain complexes I-IV (CI-CIV) occupying flatter membrane regions(1,2). Building on our recent identification of a bona fide ETC-ATP synthase supercomplex (see accompanying manuscript), here we determine how such assemblies are deployed into long-range, periodic OXPHOS arrays on native membranes. By integrating cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), we resolve multiple CIICIV2CV-based supercomplexes that act as endcaps for ATP synthase dimer (CV2) rows from the mitochondria of the kinetoplastid parasite Leishmania tarentolae. We show that repeating units of endcapped-rows stack with defined registers to tile the discoidal cristae rim, establishing a membrane-scale architectural program that couples respiratory-chain organization to cristae morphology. Subtomogram averaging validates these assemblies in situ and reveals their characteristic orientation and spacing on the crista rim. Together, these data extend the CIICIV2CV framework from molecular mechanism to mesoscale architecture and suggest that kinetoplastids achieve stable discoidal cristae by constraining ATP synthase row growth through CIICIV2CV-mediated endcapping and ordered packing.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.04.03.000172

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2026-04-04

How to Cite

Wu, M., Li, Z., Hou, Z., Tian, H., Zhang, R., Han, F., Hu, Y., Zhou, J., Li, S., Amunts, A., Liu, Y., & Zhou, L. (2026). How respiratory complexes and ATP synthase co-assemble to build cristae. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.04.03.000172

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