ArticleDiabetes2015
Diabetes Susceptibility Genes Pdx1 and Clec16a Function in a Pathway Regulating Mitophagy in β-Cells.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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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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.
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Who cites it
53 citing papers in PubMed, 79 citations in OpenAlex.
- Mitophagy and Noncoding RNA Regulation in Type 2 Diabetes Mellitus: Molecular Mechanisms, Tissue-Specific Evidence and Translational Perspective.Biomedicines · 2026Review
- Advances and challenges in the mechanistic understanding of beta-cell dysfunction in gestational diabetes mellitus.Journal of animal science · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- β-Cell Mitochondrial Dysfunction: Underlying Mechanisms and Potential Therapeutic Strategies.Cells · 2025Review
- HNF1α-Q125ter-mediated mitochondrial dysfunction and impaired mitophagy in β-cells.Journal of molecular endocrinology · 2025Article
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.eGastroenterology · 2024Article
- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- Analysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal Western-style diet during development.Frontiers in endocrinology · 2024Article
- Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal CaExperimental & molecular medicine · 2023Review
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment.Human genetics · 2023Article
- Article
- Mitochondrial regulation in human pluripotent stem cells during reprogramming and β cell differentiation.Frontiers in endocrinology · 2023Review
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
- PDX-1: A Promising Therapeutic Target to Reverse Diabetes.Biomolecules · 2022Review
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function.Journal of molecular endocrinology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mitophagy is a critical regulator of mitochondrial quality control and is necessary for elimination of dysfunctional mitochondria to maintain cellular respiration. Here, we report that the homeodomain transcription factor Pdx1, a gene associated with both type 2 diabetes and monogenic diabetes of the young, regulates mitophagy in pancreatic β-cells. Loss of Pdx1 leads to abnormal mitochondrial morphology and function as well as impaired mitochondrial turnover. High-throughput expression microarray and chromatin occupancy analyses reveal that Pdx1 regulates the expression of Clec16a, a type 1 diabetes gene and itself a key mediator of mitophagy through regulation of the E3 ubiquitin ligase Nrdp1. Indeed, expression of Clec16a and Nrdp1 are both reduced in Pdx1 haploinsufficient islets, and reduction of Pdx1 impairs fusion of autophagosomes containing mitochondria to lysosomes during mitophagy. Importantly, restoration of Clec16a expression after Pdx1 loss of function restores mitochondrial trafficking during mitophagy and improves mitochondrial respiration and glucose-stimulated insulin release. Thus, Pdx1 orchestrates nuclear control of mitochondrial function in part by controlling mitophagy through Clec16a. The novel Pdx1-Clec16a-Nrdp1 pathway we describe provides a genetic basis for the pathogenesis of mitochondrial dysfunction in multiple forms of diabetes that could be targeted for future therapies to improve β-cell function.
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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.