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Cell death

START smuggling CoQ to fight ferroptosis

Nature Cell Biology volume 25, pages 207–208 (2023)Cite this article

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Extramitochondrial coenzyme Q (CoQ) can function as a potent anti-ferroptosis radical trapper. However, it is largely unknown how CoQ is transported from mitochondria to the plasma membrane. A study now suggests that PARL-mediated STARD7 processing is responsible for the cellular distribution of CoQ.

CoQ is mainly synthesized and stored in the mitochondria of eukaryotic cells. In mitochondria, CoQ plays important roles in processes such as the electron transport chain, uridine biosynthesis and fatty acid oxidation1. A recent unexpected advancement of CoQ biology is the discovery that, via its lipophilic radical trapping activity on the plasma membrane, the reduced form of CoQ can function as an endogenous inhibitor of ferroptosis — a cell death process that is driven by iron-dependent phospholipid peroxidation and is highly relevant to metabolism and various diseases2. The CoQ oxidoreductase FSP1 is involved in this novel function of CoQ by regenerating reduced CoQ from oxidized CoQ3,4. However, this anti-ferroptotic function of CoQ raises an obvious question: as CoQ biosynthesis occurs in mitochondria and as CoQ cannot freely penetrate membranes, what is the source of plasma membrane CoQ?

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Fig. 1: PARL-mediated STARD7 processing regulates CoQ synthesis and intracellular distribution.

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Authors and Affiliations

  1. Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Deguang Liang & Xuejun Jiang

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  1. Deguang Liang
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  2. Xuejun Jiang
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Correspondence to Xuejun Jiang.

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Competing interests

D.L. is an inventor of a patent relevant to autophagy. X.J. is an inventor of patents relevant to cell death and autophagy. He is also a consultant and equity holder of Exarta Therapeutics and Lime Therapeutics.

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Liang, D., Jiang, X. START smuggling CoQ to fight ferroptosis. Nat Cell Biol 25, 207–208 (2023). https://doi.org/10.1038/s41556-022-01044-1

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  • DOI: https://doi.org/10.1038/s41556-022-01044-1

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