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Cell death

Mitophagy protects against ferroptosis

Nature Cell Biology volume 26, page 1374 (2024)Cite this article

Mitophagy, the selective autophagy of damaged mitochondria, is mediated by several receptors, including BNIP3 and NIX, and is important for mitochondrial homeostasis. Mitochondria are also the major source of reactive oxygen species (ROS); mitochondrial ROS (mtROS) can give rise to lipid peroxides, which, in turn, induce ferroptosis, a specific type of cell death. In this study, Kanki and co-workers provide direct evidence that mitophagy mediated by BNIP3 and NIX protects cells against ferroptosis by reducing mtROS.

The authors show that BNIP3 and NIX are essential for mitophagy as cells with double knockout of BNIP3 and NIX are impaired in mitophagy and exhibit reduced mitochondrial function, including reduced basal respiration and ATP production. Interestingly, these mitophagy-deficient cells are highly sensitive to ferroptosis, which can be rescued with expression of BNIP3 and NIX, or by treating cells with a mitochondrial superoxide scavenger. These findings point to an increase in mtROS levels, owing to the absence of mitophagy as an inducer of ferroptosis.

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  1. Nature Cell Biology https://www.nature.com/ncb/

    Petra Gross

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  1. Petra Gross
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Correspondence to Petra Gross.

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Gross, P. Mitophagy protects against ferroptosis. Nat Cell Biol 26, 1374 (2024). https://doi.org/10.1038/s41556-024-01507-7

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  • DOI: https://doi.org/10.1038/s41556-024-01507-7

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