ArticleScientific reports2025
Identifying a novel Mecp2-mediated epigenetic mechanism controlling Lonp1 in the hippocampus and its disruption by aging.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Reprogramming Mitochondrial Adaptation: LONP1 at the Crossroads of Proteostasis, Metabolism, and Disease.Antioxidants (Basel, Switzerland) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Aging is characterized by a progressive decline in cellular function, including the hippocampus, a brain region crucial for learning and memory. Mitochondrial dysfunction is a hallmark of aging, critical for hippocampal deterioration. The mitochondrial protease Lonp1 is a key regulator of mitochondrial proteostasis, and its diminished expression or activity has been implicated in age-related dysfunction in non-neuronal cells. However, despite its essential role in maintaining mitochondrial function, the transcriptional regulation of Lonp1 remains poorly understood. Evidence suggests that Lonp1 is subject to epigenetic control via changes in DNA methylation patterns. Mepc2, a DNA-methylation reader, acts as a transcriptional regulator highly expressed in neurons, either activating or repressing gene expression. Yet, its role in the mitochondria of aged hippocampus and its potential role as Lonp1 regulator haven't been explored. Here, we investigated Lonp1 expression and its epigenetic regulation by Mecp2 in the hippocampus of aged SAMP8 mice. We identified CpG islands in the Lonp1 promoter, near the transcription start site, where DNA methylation levels increase in aged hippocampal tissue. Chromatin immunoprecipitation revealed that Mecp2 directly binds to the Lonp1 promoter, with a significant reduction in binding observed in aged mice, correlating with increased Lonp1 mRNA levels. These findings show, for the first time, that Mecp2 is a transcriptional repressor of Lonp1 in the hippocampus. Additionally, unlike humans expressing three isoforms of Lonp1, mice exhibit only the full-length mitochondrial isoform. Interestingly, despite increased Lonp1 mRNA levels in aged mice, their protein levels were significantly decreased in the aged hippocampus. This unexpected result is, at least in part, explained by the enhanced Lonp1 protein degradation by the lysosome. Together, our findings reveal a novel mechanism that drives Lonp1 expression, linking Mecp2-mediated epigenetic regulation to age-related mitochondrial dysfunction. This study reveals Mecp2 and Lonp1 as potential therapeutic targets for mitochondrial proteostasis in aging.
Indexed as
Identifiers
What Socratic 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 Socratic graph.