Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
We investigate the role of m6A RNA methylation in regulating transcription factor EB (TFEB) and its contribution to mitochondrial autophagy (mitophagy) dysfunction in amyotrophic lateral sclerosis (ALS). ALS cell models were used to analyse mitophagy markers and TFEB expression under METTL3 and TFEB modulation, using RT-qPCR, Western blot, MeRIP, RIP, and immunofluorescence. Elevated m6A methylation and reduced TFEB expression were observed in hSOD1-G93A models. METTL3 overexpression suppressed TFEB expression, leading to impaired mitophagy, while METTL3 knockdown alleviated these effects. MeRIP assays confirmed increased m6A modifications on TFEB mRNA, and RIP assays demonstrated direct interaction between METTL3 and TFEB mRNA. Notably, TFEB overexpression rescued mitophagy dysfunction, whereas TFEB knockdown exacerbated the impairment. METTL3-mediated m6A methylation inhibits mitophagy by downregulating TFEB expression, revealing the m6A-TFEB pathway as a promising therapeutic target for ALS.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ajmg.b.33048 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging.
Aging Cell
September 2025
Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
While BAG3 has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in BAG3-related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish bag3 cardiomyopathy model. Given the known cardioprotective effects of mtor inhibition and the fact that transcription factor EB (tfeb) encodes a direct downstream phosphorylation target of mTOR signaling, we generated a cardiomyocyte-specific transgenic line overexpressing tfeb (Tg[cmlc2:tfeb]).
View Article and Find Full Text PDFDeletion of ABIN1-LIR motifs impairs hepatic lipid homeostasis and mitophagy via AMPK-TFEB axis in mice.
Am J Physiol Cell Physiol
September 2025
Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany.
The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.
View Article and Find Full Text PDF20-Deoxyingenol attenuated doxorubicin-induced cardiotoxicity by promoting autolysosome degradation through the UCHL3-TFEB pathway.
Phytomedicine
September 2025
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart
Background: Impaired autophagic flux is an essential contributor to doxorubicin (DOX)-induced cardiotoxicity (DIC). TFEB is recognized as a key regulator of DOX-induced autolysosome accumulation; however, the mechanisms by which DOX suppresses TFEB expression remain unclear. 20-Deoxyingenol (20-DOI) is a small-molecule compound whose potential protective effects against DIC has not yet been elucidated.
View Article and Find Full Text PDFNeurons sequester the cholesterol-inhibiting TFEB in oligodendrocyte cytoplasm to safeguard myelination and neural function.
Cell Rep
September 2025
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern M
Myelination is essential for normal brain function, yet the mechanisms governing neuron-oligodendrocyte interactions that ensure proper myelination levels remain poorly understood. Here, we identify transcription factor EB (TFEB) as a molecular link that connects extrinsic neuronal cues to intrinsic oligodendrocyte transcriptional programs, regulating central nervous system myelination. Using a TFEB epitope-tagged knock-in mouse model, we find that neurons sequester most of the TFEB protein in the cytoplasm of myelinating oligodendrocytes.
View Article and Find Full Text PDFBisphenol F disrupts lipophagy and lysosomal acidification via ATGL-SIRT1-PPARα signaling in NAFLD-like hepatic changes.
Ecotoxicol Environ Saf
September 2025
Center for Global Health, the Key Laboratory of Modern Toxicology, Ministry of Education, Department of Hygienic Analysis and Detection, School of Public Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Bisphenol F (BPF), a widely used substitute for bisphenol A (BPA), has raised growing concerns due to its potential metabolic toxicity. Recent studies suggest that BPF exposure is associated with lipid accumulation and non-alcoholic fatty liver disease (NAFLD)-like changes, however, the underlying mechanisms remain poorly understood. This study was performed to investigate the BPF-induced NAFLD-like changes through the lipid degradative pathway, which via an unrecognized defect of lipophagy mediated by Adipose Triglyceride Lipase (ATGL)-Sirtuin 1 (SIRT1)-Peroxisome proliferator-activated receptor α (PPARα) signaling axis.
View Article and Find Full Text PDF