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bioRxiv · 10.1101/2021.05.04.442683

Heme oxygenase limits mycobacterial infection-induced ferroptosis

Luo, K.·Stocker, R.·Britton, W. J. J.·Kikuchi, K.·Oehlers, S. H.
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Abstract

Iron homeostasis is essential for both sides of the host-pathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary co-factor for host immunity. Heme oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of heme. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different host-pathogen combinations. Here we use the natural host-pathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish heme oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from mycobacterial infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against mycobacterial infection by reducing infection-induced iron accumulation and ferroptosis.

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Luo, K., Stocker, R., Britton, W. J. J., Kikuchi, K., Oehlers, S. H.. 2021-05-04. Heme oxygenase limits mycobacterial infection-induced ferroptosis. https://doi.org/10.1101/2021.05.04.442683

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