ArticleNature communications2022
Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 97 citations in OpenAlex.
- A high-confidence inventory of the proteins in the mitochondrion-related organelle of Giardia.Current biology : CB · 2026Article
- Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.Nature metabolism · 2026Article
- Mechanical stress promotes excessive NETs and exacerbates acute lung injury via Piezo1-mediated mitochondrial dysfunction.Redox biology · 2026Article
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Inhibition of ferroptosis via SLC25A39-NRF2 axis drives Osimertinib resistance in lung adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Technology-enabled insights into SLC transporters in MAFLD: redefining the multi-hit pathogenesis and therapeutic landscape.Acta pharmacologica Sinica · 2026Review
- Structural evolution of the MTCH family of mitochondrial insertases.Science advances · 2026Article
- Structural evolution of the MTCH family of mitochondrial insertases.bioRxiv : the preprint server for biology · 2026Article
- Nrp1 Signaling Reprograms Glutathione Metabolism to Drive Mitochondrial Dysfunction in Severe Asthma.Antioxidants (Basel, Switzerland) · 2026Article
- From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026Review
- Behavioral screening defines the molecular Parkinsonism-related subgroups in Drosophila.Nature communications · 2026Article
- SLC25 in intestinal inflammation: mechanisms, pathological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- Targeting Ferroptosis for Cerebral Neuroprotection in Ischemic Stroke: Pathophysiological Insights.International journal of general medicine · 2026Review
- Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling.Cancer discovery · 2025Article
- Mitochondrial glutathione transporter SLC25A40 regulates macrophage cytokine production.Scientific reports · 2025Article
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- SLC25A39 regulates Hedgehog signaling to promote tumor progression and sorafenib resistance in hepatocellular carcinoma.Scientific reports · 2025Article
- Glutamine-Dependent Slc25a39-Nrf2 Axis Couples Mitochondrial Dynamics with Metabolic Reprogramming to Establish Myogenic Commitment.bioRxiv : the preprint server for biology · 2025Article
- FGF21 maintains redox homeostasis and promotes neuronal survival after traumatic brain injury by targeting SLC25A39-mediated mitochondrial GSH transport.Journal of translational medicine · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes. The family is highly redundant and their transport activities coupled to metabolic state. Here, we use a pooled, dual CRISPR screening strategy that knocks out pairs of transporters in four metabolic states - glucose, galactose, OXPHOS inhibition, and absence of pyruvate - designed to unmask the inter-dependence of these genes. In total, we screen 63 genes in four metabolic states, corresponding to 2016 single and pair-wise genetic perturbations. We recover 19 gene-by-environment (GxE) interactions and 9 gene-by-gene (GxG) interactions. One GxE interaction hit illustrates that the fitness defect in the mitochondrial folate carrier (SLC25A32) KO cells is genetically buffered in galactose due to a lack of substrate in de novo purine biosynthesis. GxG analysis highlights a buffering interaction between the iron transporter SLC25A37 (A37) and the poorly characterized SLC25A39 (A39). Mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis identify A39 as critical for mitochondrial glutathione (GSH) import. Functional studies reveal that A39-mediated glutathione homeostasis and A37-mediated mitochondrial iron uptake operate jointly to support mitochondrial OXPHOS. Our work underscores the value of studying family-wide genetic interactions across different metabolic environments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.