ArticleDiabetes & metabolism journal2024
PDZD8 Augments Endoplasmic Reticulum-Mitochondria Contact and Regulates Ca2+ Dynamics and Cypd Expression to Induce Pancreatic β-Cell Death during Diabetes.
Article in Diabetes & metabolism journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Mitochondria‑associated endoplasmic reticulum membranes in degenerative musculoskeletal disorders: Mechanistic evidence and therapeutic perspectives (Review).Molecular medicine reports · 2026Review
- Research Progress on Downstream Mechanisms of Glucose Metabolic Reprogramming and Its Role in the Occurrence and Progression of Type 2 Diabetes Mellitus.Biomedicines · 2026Review
- PDZD8 overexpression alleviates early brain injury via regulating MERCs integrity after experimental subarachnoid hemorrhage.Journal of neuroinflammation · 2026Article
- Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation.Cell communication and signaling : CCS · 2026Review
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- Alzheimer's disease: disrupted communication between the endoplasmic reticulum and mitochondria.Journal of neurology · 2026Review
- The spatiotemporal dynamics of MAMs: mechanisms, pathologies, and therapeutic rewiring.Cellular & molecular biology letters · 2026Review
- Mitochondria-associated membranes in heart failure: from molecular mechanisms to therapeutic targets.Frontiers in physiology · 2026Review
- Long-chain saturated free fatty acids induce pancreatic β-cell lipotoxic stress via HFrontiers in endocrinology · 2026Article
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Tangled contacts: mitochondrial interactions with cellular organelles in acute pancreatitis.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Tanshinone IIA ameliorates pancreatic injury in type 2 diabetic mice by modulating inflammation and endoplasmic reticulum stress via the IL-6/JAK2/STAT3 pathway.Functional & integrative genomics · 2025Article
- Inhibition of STING-induced mitochondrial Drp1/N-GSDMD-mediated MtDNA release alleviates Sepsis-induced lung injury.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Mitochondrial complexity is regulated at ER-mitochondria contact sites via PDZD8-FKBP8 tethering.Nature communications · 2025Article
- Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice.Molecular autism · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
backgruoundDiabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action.
methodsHigh-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit.
resultsPDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells.
conclusionPDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.
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