ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed.
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- Ginsenosides: potential therapeutic implications in neurodegenerative diseases by inhibiting ferroptosis.Molecular biology reports · 2026Review
- Advances in the Core Role and Mechanisms of Mitochondrial Dysfunction in Alzheimer's Disease.Brain and behavior · 2026Review
- Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can Natural SIRT1 Activators Be Therapeutic Allies in the Inflammation-Energy Axis?Phytotherapy research : PTR · 2026Review
- Cytoprotective Mechanism of Necrox-5 Against Toxicity Induced by Experimental Ferroptosis Instigators and the Pesticide Propargite.International journal of molecular sciences · 2026Article
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
- Insights into cytotoxicity and redox modulation by the herbicide linuron and its metabolite, 3,4-dichloroaniline.Neurotoxicology · 2025Article
- Inhibition of Ferroptotic Toxicity by 4-Hydroxyindole.Chemical research in toxicology · 2025Article
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
18 authors.
Funding
Abstract
Alzheimer's disease (AD) is defined by β-amyloid plaques and tau-containing neurofibrillary tangles, but the ensuing cellular derangements that culminate in neurodegeneration remain elusive. Here, a mechanistic link between two AD pathophysiological hallmarks: energy insufficiency and oxidative stress is revealed. It is demonstrated that mitochondrial function and glutathione (GSH) flux are coupled, impacting neuronal ferroptosis susceptibility. Analysis of proteomic data from the inferior temporal cortex of 625 subjects along a continuum of clinical and pathological changes in AD, reveals a prominent depletion of mitochondrial proteins. Biogenetic insufficiency in AD is reflected by a concurrent loss of GSH, which requires 2 ATP for its synthesis, and genetic and pharmacologic ATP depletion models confirm that ATP is rate-limiting for GSH. Accordingly, an unbiased association analysis uncovers mitochondrial proteins in positive correlation with total GSH (t-GSH) in AD subjects. But mitochondria also consume GSH via the SLC25A39 transporter. It is found that mitochondrial inhibition either increases or decreases ferroptosis susceptibility in cellular models, depending on contextual factors that dictate whether mitochondria act as a net GSH producer or consumer, respectively. Mitochondria therefore control GSH flux, and loss of energy output is consequently demonstrated as a liability for ferroptosis in AD.
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.