PXD082345

PXD082345 is an original dataset announced via ProteomeXchange.

Title	Cysteine excess triggers a mitochondrial iron-dependent cell death
Description	Thiol-containing metabolites are central to cellular redox homeostasis1. Among these, cysteine functions as a proteogenic amino acid, supports redox balance and iron–sulfur cluster biogenesis, and, when depleted, triggers ferroptosis2. Cells nevertheless maintain cysteine at low levels, reflecting its intrinsic toxicity, but the mechanisms by which excess cysteine causes cell death remain unclear3. Here, we performed a genome-wide CRISPR screen and identified mitochondrial iron transporters as essential mediators of cysteine toxicity. Limiting mitochondrial iron availability suppresses cysteine-induced cell death and prevents impairment of iron–sulfur cluster proteins and respiration. Mechanistically, cysteine mobilizes iron from ferritin, expands cytosolic iron pool, and drives mitochondrial iron accumulation. Enhancing glutathione reductase activity specifically within mitochondria restores redox balance downstream of iron accumulation and protects cells by maintaining iron–sulfur cluster integrity. Our findings suggest that maintaining low cysteine levels safeguards mitochondrial iron homeostasis, and that excess cysteine triggers a distinct mitochondrial iron-dependent cell death under conditions of thiol imbalance.
HostingRepository	PRIDE
AnnounceDate	2026-08-14
AnnouncementXML	Submission_2026-08-14_08:42:43.352.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Toshitaka Nakamura
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-07 11:53:16	ID requested
⏵ 1	2026-08-14 08:42:43	announced

Dataset with its publication pending

submitter keyword: Cysteine, Cell death, Iron

Kivanc Birsoy
contact affiliation	The Rockefeller University
contact email	kbirsoy@rockefeller.edu
lab head
Toshitaka Nakamura
contact affiliation	The Rockefeller University
contact email	toshitaka.nakamura@rockefeller.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD082345
     1. Label: PRIDE project
     2. Name: Cysteine excess triggers a mitochondrial iron-dependent cell death