ArticleAutophagy2023
Impaired TFEB activation and mitophagy as a cause of PPP3/calcineurin inhibitor-induced pancreatic β-cell dysfunction.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- A real-world investigation of drug-induced hyperglycemia and diabetes mellitus in pediatric populations using the FDA adverse event reporting system.Frontiers in medicine · 2026Article
- Tacrolimus inhibits CVB3-targeted regulation of TFEB by PPP3/calcineurin.Frontiers in cellular and infection microbiology · 2026Article
- Review
- [The miR-30b/USP14 axis regulates mitophagy via a non-PINK1/Parkin pathway in neuronal oxygen-glucose deprivation/reoxygenation injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial quality control in diabetes mellitus and complications: molecular mechanisms and therapeutic strategies.Cell death & disease · 2025Review
- Transcription factor EB improves hypoxic pulmonary hypertension in fetal rats by suppressing NLRP3 inflammasome activation via induction of mitophagy.Scientific reports · 2025Article
- Rescuing vascular dysfunction in dorsal pancreatic arteries prevents tacrolimus-induced glucose metabolism disorder in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Extracellular Vesicles and Immune Activation in Solid Organ Transplantation: The Impact of Immunosuppression.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- GADD45α is a direct target of TFEB and contributes to tacrolimus-induced chronic nephrotoxicity.JCI insight · 2025Article
- Natural small molecules regulating the mitophagy pathway counteract the pathogenesis of diabetes and chronic complications.Frontiers in pharmacology · 2025Review
- Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay.Scientific reports · 2024Article
- Review
- Far-Red Fluorescent Proteins: Tools for Advancing In Vivo Imaging.Biosensors · 2024Review
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal CaExperimental & molecular medicine · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy or mitophagy plays crucial roles in the maintenance of pancreatic β-cell function. PPP3/calcineurin can modulate the activity of TFEB, a master regulator of lysosomal biogenesis and autophagy gene expression, through dephosphorylation. We studied whether PPP3/calcineurin inhibitors can affect the mitophagy of pancreatic β-cells and pancreatic β-cell function employing FK506, an immunosuppressive drug against graft rejection. FK506 suppressed rotenone- or oligomycin+antimycin-A-induced mitophagy measured by Mito-Keima localization in acidic lysosomes or RFP-LC3 puncta colocalized with TOMM20 in INS-1 insulinoma cells. FK506 diminished nuclear translocation of TFEB after treatment with rotenone or oligomycin+antimycin A. Forced TFEB nuclear translocation by a constitutively active TFEB mutant transfection restored impaired mitophagy by FK506, suggesting the role of decreased TFEB nuclear translocation in FK506-mediated mitophagy impairment. Probably due to reduced mitophagy, recovery of mitochondrial potential or quenching of mitochondrial ROS after removal of rotenone or oligomycin+antimycin A was delayed by FK506. Mitochondrial oxygen consumption was reduced by FK506, indicating reduced mitochondrial function by FK506. Likely due to mitochondrial dysfunction, insulin release from INS-1 cells was reduced by FK506 in vitro. FK506 treatment also reduced insulin release and impaired glucose tolerance in vivo, which was associated with decreased mitophagy and mitochondrial COX activity in pancreatic islets. FK506-induced mitochondrial dysfunction and glucose intolerance were ameliorated by an autophagy enhancer activating TFEB. These results suggest that diminished mitophagy and consequent mitochondrial dysfunction of pancreatic β-cells contribute to FK506-induced β-cell dysfunction or glucose intolerance, and autophagy enhancement could be a therapeutic modality against post-transplantation diabetes mellitus caused by PPP3/calcineurin inhibitors.
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