OXPHOS

Promoting Biotechnology and Drug Discoveries
  • Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587

    Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation ofMycobacterium tuberculosisby inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with eitherM. tuberculosisATP synthase or human ATP synthase is unclear. Here we pr...

  • Structure of the human ATP synthase

    Biological energy currency ATP is produced by F1Fo-ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures reveal that the release of ADP occurs when the β subunit of F1Fo-ATP syntha...

  • Structure of the human respiratory complex II

    Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of thi...

  • An electron transfer path connects subunits of a mycobacterial respiratory supercomplex

    This study of a respiratory supercomplex in Mycobacteria reveals cofactors positioned at distances that permit electron tunneling, enabling direct intrasupercomplex electron transfer from menaquinol to oxygen without the need for a separate cytochrom

RESEARCH ARTICLE

Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides Bridges HR, Blaza JN, Yin Z, Chung I, Pollak MN, Hirst J 2024-07-11 Science
High-resolution in situ structures of mammalian respiratory supercomplexes Wan Zheng, Pengxin Chai, Jiapeng Zhu & Kai Zhang 2024-07-11 Nature
Manipulating mitochondrial electron flow enhances tumor immunogenicity 2023-09-23 Science
Structure of the human ATP synthase 2023-05-29 Molecular Cell
Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds 2023-04-13 Science
Mitochondria metabolism sets the species-specific tempo of neuronal development 2023-04-13 Science

NEWS & VIEWS

RESEARCH INTEREST

Our research interests mainly focus on the oxidative phosphorylation (OXPHOS) system.

OXPHOS system is central to cellular metabolism. It comprises five enzymatic complexes (CI, CII, CIII, CIV, CV) and two mobile electron carriers (Q, Cyt C) that work in a respiratory chain (CI, CII, CIII, CIV, Q, Cyt C). By coupling the oxidation of reducing equivalents to the generation and subsequent dissipation of a proton gradient across the inner mitochondrial or cellular membrane, this electron transport chain (CI, CII, CIII, CIV, Q, Cyt C) drives the production of ATP through the CV, which is then used as a primary energy carrier in virtually all cellular processes. Minimal perturbations of the respiratory chain activity are linked to pathogen growth and host diseases; therefore, it is necessary to understand how these complexes are assembled and regulated and how they function. Most encouragingly, these membrane-bound complexes are also being exploited as drug targets in curing human cancer and other diseases, and against the pathogen infections.



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