ArticleProceedings of the National Academy of Sciences of the United States of America2019
DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 2 of them syntheses that pooled it.
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Who cites it
174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 279 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Calcium overload-induced apoptosis in cancer cells: ER-mitochondria crosstalk and therapeutic implications.Pharmaceutical science advances · 2026Review
- Mitochondrial Localization of Cx26 Promotes Colorectal Cancer Malignancy and Exposes a Fatal Vulnerability to Drug Targeting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Effects of homozygous PARK7 gene mutations L166P and M26I on BNIP3/BNIP3L interactions and ER-mitochondria proximity.Biology direct · 2026Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Intermembrane coupling between Bcl-xL and the IPCell reports · 2026Article
- Neuronal DJ-1 regulates microglial activation in Parkinson's disease.Neural regeneration research · 2026Article
- Redox control at the ER-mitochondria interface in kidney transplantation: MAM-centered stress signaling and translational organoid platforms.Redox biology · 2026Review
- Mitochondria-Associated Endoplasmic Reticulum Membranes in Cancer: Hubs for Tumor Progression and Therapeutic Vulnerabilities.Cell biology international · 2026Review
- Mitochondrial Voltage-Dependent Anion Channel: From a Passive Pore to a Cellular Hub Through Protein Complexation.International journal of molecular sciences · 2026Review
- A prognostic model for breast cancer based on mitochondria-associated endoplasmic reticulum membrane (MAM) signature genes.Discover oncology · 2026Article
- Excessive ER-mitochondria coupling: A DRP1-driven mechanism underlying mitochondrial dysfunction and impaired autophagy in stress-induced depression-like behavior in mice.Redox biology · 2026Article
- Spatiotemporal Ca2+ nanodomain remodeling at MERCS regulates mitochondrial proteostasis.Protein & cell · 2026Article
- Mitochondrial interplay with membrane organelles in health and disease.Cell communication and signaling : CCS · 2026Review
- Parkinson's disease-associated PLA2G6 protects IP3R1 protein to control ER-mitochondria tethering and CaNature communications · 2026Article
- The spatiotemporal dynamics of MAMs: mechanisms, pathologies, and therapeutic rewiring.Cellular & molecular biology letters · 2026Review
114 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Loss-of-function mutations in DJ-1 are associated with autosomal recessive early onset Parkinson's disease (PD), yet the underlying pathogenic mechanism remains elusive. Here we demonstrate that DJ-1 localized to the mitochondria-associated membrane (MAM) both in vitro and in vivo. In fact, DJ-1 physically interacts with and is an essential component of the IP3R3-Grp75-VDAC1 complexes at MAM. Loss of DJ-1 disrupted the IP3R3-Grp75-VDAC1 complex and led to reduced endoplasmic reticulum (ER)-mitochondria association and disturbed function of MAM and mitochondria in vitro. These deficits could be rescued by wild-type DJ-1 but not by the familial PD-associated L166P mutant which had demonstrated reduced interaction with IP3R3-Grp75. Furthermore, DJ-1 ablation disturbed calcium efflux-induced IP3R3 degradation after carbachol treatment and caused IP3R3 accumulation at the MAM in vitro. Importantly, similar deficits in IP3R3-Grp75-VDAC1 complexes and MAM were found in the brain of DJ-1 knockout mice in vivo. The DJ-1 level was reduced in the substantia nigra of sporadic PD patients, which was associated with reduced IP3R3-DJ-1 interaction and ER-mitochondria association. Together, these findings offer insights into the cellular mechanism in the involvement of DJ-1 in the regulation of the integrity and calcium cross-talk between ER and mitochondria and suggests that impaired ER-mitochondria association could contribute to the pathogenesis of PD.
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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.