ReviewAntioxidants (Basel, Switzerland)2025
The Ferroptosis-Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation.
Review in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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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
37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.Frontiers in immunology · 2026Pooled it
- Antidepressant effects and therapeutic potential of naringenin: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2026Pooled it
- Transcriptomic analysis reveals and validates lipid raft-associated biomarkers and functional networks in Alzheimer's disease.IBRO neuroscience reports · 2026Article
- Exercise-induced neuropeptidergic and neurochemical neuroadaptation in stress regulation and emotional disorders.Acta neurologica Belgica · 2026Review
- Neuroinflammation, HPA Axis Dysregulation, Cytokine Activity and Nutritional Modulation in Depression: A PRISMA-compliant Systematic Review.Annals of neurosciences · 2026Review
- Lentinan Improves Sodium Arsenite-Induced Hepatic Lipid Accumulation and Ferroptosis: Role of AMPK Signaling Pathway.Toxics · 2026Article
- Clemastine ameliorates ulcerative colitis-induced cognitive impairment by restoring PI3K/Akt/GSK-3β signaling and suppressing ferroptosis.Inflammopharmacology · 2026Article
- Integrated biomarkers of oxidative stress NLRP3 inflammasome and kynurenine pathway reflect disease severity and diagnostic discrimination in depression.Scientific reports · 2026Article
- Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts.Antioxidants (Basel, Switzerland) · 2026Article
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Metabolic Adaptation in Acute Ischemic Events: The Critical Role of Acyl-Coenzyme A Synthetase Family in Myocardial Infarction and Ischemic Stroke.Journal of the American Heart Association · 2026Review
- An engineered ROS-responsive cascade nanoplatform delays Alzheimer's disease progression via Nrf2/GPX4-mediated microglial functional reprogramming.Materials today. Bio · 2026Article
- Anti-HMGB1 Antibody Therapy Ameliorates Depression Following Spinal Cord Injury in Rats by Inhibiting Ferroptosis.Journal of cellular and molecular medicine · 2026Article
- Molecules of mood: the integrated molecular transducers of exercise's antidepressant effects.Molecular genetics and genomics : MGG · 2026Review
- The Crosstalk Mechanisms Between Ferroptosis and Pyroptosis and Their Applications in Diseases: From Molecular Networks to Clinical Strategies.Journal of cellular and molecular medicine · 2026Review
- Mitochondrial Iron Handling and Lipid Peroxidation as Drivers of Ferroptosis.International journal of molecular sciences · 2026Review
- Neuro-inflammation Induced by Arsenic: An Insight into Mechanisms and Pathways Involved.Biological trace element research · 2026Review
- The Relationship Between Trace Elements and Depression.Nutrients · 2026Review
- Role of Microglial Dysfunction in Parkinson's Disease: From Multifactorial Causes to Neurodegeneration.Neuroscience bulletin · 2026Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Emerging evidence links ferroptosis-mitochondrial dysregulation to depression pathogenesis through an oxidative stress-energy deficit-neuroinflammation cycle driven by iron overload. This study demonstrates that iron accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating an AMPK/mTOR signaling imbalance and calcium dyshomeostasis that synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: lipid peroxidation derivatives oxidize mitochondrial cardiolipin, while mitochondrial ROS overproduction activates ACSL4 to amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal-hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing mitochondrial biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show that microglial M1 polarization through cGAS-STING activation sustains neuroinflammation via IL-6/TNF-α release. We propose a "ferroptosis-mitochondrial fragmentation-metabolic maladaptation" triad as mechanistic subtyping criteria for depression. Preclinical validation shows that combinatorial therapy (iron chelators + SIRT3 agonists) rescues neuronal viability by restoring mitochondrial integrity and energy flux. This work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing iron homeostasis, organelle dynamics, and metabolic vulnerability-a framework with significant implications for developing neuroprotective antidepressants.
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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.