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NLRX1 is an essential, druggable regulator of mitochondrial permeability transition

Rachel E. Peltier-Heap David W. Frederick R. Pickering Sonja Ghidelli-Disse Kirsten Searle Juliette C. Barber Nicholas Galwey Léa P. Wilhelm K. Triantafilou M. Triantafilou Oliver Wright Sumitra Ramachandran Yang Tan Wen-Hao Xia Chiu-Cheong Aw Pamela P. Oon Emma L. Rivers K. Lee Yannick M L Lacroix E. Reddy Robert P. Glover Gino Brunori Ashley J. Broom D. Grimsditch Annie Garcia A. Robertson Kazufumi Hirano Angela A. Brady Edward R. Browne G. Drewes Ian G. Ganley K. Schroder M. Ahmed Lee M. Booty

Aug 2026 · bioRxiv · 0 citations · 52 references

Biology

TL;DR

NLRX1 is established as an essential, CypD-independent regulator of mitochondrial permeability transition and provide brain-penetrant chemical tools to interrogate this biology.

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NLRX1 emerges as the only observed essential regulator of the mPTP, challenging mPTP inhibition as a valid target of cardioprotection.

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Chemoproteomic discovery of a brain-penetrant, covalent NLRP3 inhibitor that binds a novel allosteric pocket.

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