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Bridges HR, Blaza JN, Yin Z, Chung I, Pollak MN, Hirst J
Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides
The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo–electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide ...
Science | 2024-07-11
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Wan Zheng, Pengxin Chai, Jiapeng Zhu & Kai Zhang
High-resolution in situ structures of mammalian respiratory supercomplexes
Mitochondria play a pivotal part in ATP energy production through oxidative phosphorylation, which occurs within the inner membrane through a series of respiratory complexes1,2,3,4. Despite extensive in vitro structural studies, determining the atomic details of their molecular mechanisms in physiological states remains a major challenge, primarily because of loss of the native environment du...
Nature | 2024-07-11
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Manipulating mitochondrial electron flow enhances tumor immunogenicity
In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell–mediated killing.
Science | 2023-09-23
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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...
Molecular Cell | 2023-05-29
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Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds
Loss leads to gainHummingbirds display true hovering flight, an incredibly energy-intensive activity. Although much is known about the physiology of this movement, little has been known about the genetics underlying its evolution. Osipovaet al. screened newly generated and previously sequenced bird genomes to search for key changes facilitating this high-energy locomotion. They found that a g...
Science | 2023-04-13
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Mitochondria metabolism sets the species-specific tempo of neuronal development
Metabolism sets neuronal development paceThe pace of neuronal development varies between species, and the relatively slow development of the human brain may help allow its exceptional complexity. Iwataet al. propose that the pace of neuronal development depends on the rate of metabolic activity in mitochondria. Human and mouse neurons exhibited distinct paces of development in culture correlat...
Science | 2023-04-13