ArticleMolecular cell2024
Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 40 citations in OpenAlex.
- Enzymatic/Mitochondrial Import Bottleneck in Sepsis with Possible Extensions to DIC: IV Glutathione and Hinokitiol as Potential Therapeutic Candidates.International journal of molecular sciences · 2026Article
- Article
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- The iron-sulfur cluster assembly factor FDX2 is required for tumor initiation but not for growth of established tumors in transplantation models.The Journal of biological chemistry · 2026Article
- Loss of Function of AFG3L2 Leading to Developmental and Epileptic Encephalopathy.CNS neuroscience & therapeutics · 2026Article
- Cysteine imaging reveals early redox dysregulation and identifies gnetol as a ferroptosis-modulating agent in doxorubicin cardiotoxicity.Redox biology · 2026Article
- Nrp1 Signaling Reprograms Glutathione Metabolism to Drive Mitochondrial Dysfunction in Severe Asthma.Antioxidants (Basel, Switzerland) · 2026Article
- Identifying a cancer therapeutic target: Cell-SELEX identifies a membrane protein for aptamer-mediated growth suppression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Physalin F Promotes AFG3L2-Mediated Degradation of VISA/MAVS to Suppress Innate Immune Response to RNA Virus.Pathogens (Basel, Switzerland) · 2026Article
- SLC25A mitochondrial carriers as biomarkers and therapeutic targets of spaceflight-induced dysfunction: the ADP/ATP carrier (AAC3) as a structural case study.Journal of translational medicine · 2025Article
- SLC25A39 identified as a key regulator of hepatocellular carcinoma progression through the mitochondrial ROS-cytochrome c-caspase signaling axis.Cellular & molecular biology letters · 2025Article
- Mitochondrial glutathione transporter SLC25A40 regulates macrophage cytokine production.Scientific reports · 2025Article
- SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis.Molecular cell · 2025Article
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 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
- PEX5 deficiency enhances radiosensitivity via MGST1-GSH detoxifying function and promotes ferroptosis in liver cancer.Science China. Life sciences · 2025Article
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SLC25A39 overexpression exacerbates lung adenocarcinoma progression and is negatively regulated by AFG3L2.NPJ precision oncology · 2025Article
- The GLYT1 inhibitor bitopertin mitigates erythroid PPIX production and liver disease in erythroid protoporphyria.The Journal of clinical investigation · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Organelle transporters define metabolic compartmentalization, and how this metabolite transport process can be modulated is poorly explored. Here, we discovered that human SLC25A39, a mitochondrial transporter critical for mitochondrial glutathione uptake, is a short-lived protein under dual regulation at the protein level. Co-immunoprecipitation mass spectrometry and CRISPR knockout (KO) in mammalian cells identified that mitochondrial m-AAA protease AFG3L2 is responsible for degrading SLC25A39 through the matrix loop 1. SLC25A39 senses mitochondrial iron-sulfur cluster using four matrix cysteine residues and inhibits its degradation. SLC25A39 protein regulation is robust in developing and mature neurons. This dual transporter regulation, by protein quality control and metabolic sensing, allows modulating mitochondrial glutathione level in response to iron homeostasis, opening avenues for exploring regulation of metabolic compartmentalization. Neuronal SLC25A39 regulation connects mitochondrial protein quality control, glutathione, and iron homeostasis, which were previously unrelated biochemical features in neurodegeneration.
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.