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Article

Deep Mutational Scanning of FDX1 Identifies Key Structural Determinants of Lipoylation and Cuproptosis.

Nature communications - 21 Dec 2025

Hsiao Jeffrey C, Warui Douglas M, Kwon Jason J, Dreishpoon Margaret B, Bick Nolan R, Blue-Lahom Tamra, Root David E, Booker Squire J, Tsvetkov Peter

Abstract excerpt

Cuproptosis is a recently described form of regulated cell death triggered by ionophore-induced copper (Cu) overload in mitochondria. It is critically dependent on ferredoxin 1 (FDX1), a mitochondrial iron-sulfur cluster containing protein that acts as an electron shuttle. FDX1 reduces ionophore-bound Cu(II) to Cu(I), thereby triggering its release, and promotes mitochondrial protein lipoylation, which is...

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Identifiers

PMID: 41423452
DOI: 10.1038/s41467-025-67869-0
PMCID: PMC12855868

Genes

FDX1
DLD

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

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