ArticleSignal transduction and targeted therapy2026
Targeting ATP11B-YAP axis repairs mitochondrial function and inhibits neuronal ferroptosis to attenuate age-related cognitive decline.
Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
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10 authors.
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Abstract
Brain aging is accompanied by cognitive decline and an increased risk of neurodegenerative disease, with neuronal aging being a key causative factor. Studies have shown that the earliest damage to blood-brain barrier (BBB) integrity occurs in the hippocampus, leading to the abnormal accumulation of Fe²⁺;however, the mechanisms underlying subsequent neuronal aging remain unclear. Using single-cell and spatial transcriptomic analyses, this study focuses on the phospholipid flippase ATP11B. We found that ATP11B deficiency facilitates the transport of Fe²⁺ from ependymal cells to hippocampal neurons, activating the Hippo signaling pathway and inducing mitochondrial respiratory dysfunction and dynamic imbalance, which results in neuronal ferroptosis and exacerbation of aging phenotypes. Mechanistically, ATP11B blocks mitochondrial respiratory function by regulating the chromatin accessibility of KLF4 to mitochondrial respiratory chain complex genes. Simultaneously, it impairs the mitochondrial quality control system, resulting in elevated levels of reactive oxygen species(ROS) and enhanced neuronal aging. The mitochondria-associated metabolite, lactate, facilitates histone lactylation of ferroptosis and the key aging-related genes Acsl4, Trp53 and Cdkn1a via the TEAD-YAP complex, thereby promoting transcription. This research uncovers the molecular mechanism through which ATP11B mediates neuronal aging: regulating the iron transport-mitochondrial plasticity axis. This provides a novel avenue for targeting iron homeostasis to intervene in cognitive decline and neurodegenerative disease.
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