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Metabolism

Plugging the leak

Nature Chemical Biology volume 11, pages 831–832 (2015)Cite this article

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Multiple mitochondrial components generate reactive oxygen species (ROS), but separating the consequences of each ROS-generating source from overall mitochondrial health is challenging. A new class of small-molecule inhibitors that selectively block ROS generation from one of the most active sources may provide a new approach toward achieving that goal.

Mitochondria serve as the powerhouse of the cell by oxidizing glycolytic products to generate ATP. The redox energy is transmitted through the four complexes of the electron transport chain and ultimately transferred to molecular oxygen. The system is imperfect as an electron shuttle, and rogue electrons 'leak' from multiple sites in the chain, generating incompletely reduced oxygen byproducts referred to as ROS2. ROS have been implicated in mediating diverse disease states by overwhelming the redox buffering capacity of the cell, ultimately damaging biomolecules3. The imperfection of electron transport and resultant ROS leakage from mitochondria has intrigued researchers for decades and helps form the basis for the free radical theory of aging4. Mitochondrial ROS generation could be a consequence of the physical limits of efficiency of biological electron transport, but, more interestingly, it suggests that ROS generation actually provides an evolutionary fitness advantage5,6.

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Figure 1: Schematic of function of S3QELs.

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  1. Bryan C. Dickinson is in the Department of Chemistry, The University of Chicago, Chicago, Illinois, USA.,

    Bryan C Dickinson

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  1. Bryan C Dickinson
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Correspondence to Bryan C Dickinson.

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Dickinson, B. Plugging the leak. Nat Chem Biol 11, 831–832 (2015). https://doi.org/10.1038/nchembio.1934

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