ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers, 3 of them syntheses that pooled it.
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Who cites it
331 citing papers in PubMed, 3 syntheses or guidelines pooled it, 555 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Current perspectives and trends on the role of mitochondria in renal ischemia-reperfusion injury from 2005 to 2024: a bibliometric analysis and literature review.Frontiers in physiology · 2025Pooled it
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Mitofusin 2 orchestrates mitochondrial metabolic homeostasis and suppresses cutaneous squamous cell carcinoma by stabilizing ER-mitochondria contacts.Journal of bioenergetics and biomembranes · 2026Article
- Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension.Journal of human hypertension · 2026Article
- Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.Neural regeneration research · 2026Article
- Mitochondria-Endoplasmic Reticulum Crosstalk in Pancreatic β-Cell Stress: A Driver of Diabetes.Cells · 2026Review
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Advanced imaging of membrane contact sites.Nature cell biology · 2026Review
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Mitochondrial-endoplasmic reticulum interactions in lung diseases.Cell death & disease · 2026Review
- Mitochondria-Associated Endoplasmic Reticulum Membranes in Cancer: Hubs for Tumor Progression and Therapeutic Vulnerabilities.Cell biology international · 2026Review
- Crosstalk between endoplasmic reticulum stress and mitochondrial homeostasis: A new perspective on ophthalmic disease treatment.Journal of cell communication and signaling · 2026Review
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis.Journal of advanced research · 2026Article
- Bridging nanomechanics and bioenergetics of single mitochondria by atomic force microscopy.Life science alliance · 2026Article
- Molecular Biomarkers of Training Responses: A Systems Framework for Exercise Adaptation and Athlete Monitoring.International journal of molecular sciences · 2026Review
- Natural photosynthetic system for restoring homeostasis of animal organelle interaction network.Nature communications · 2026Article
- STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria.The EMBO journal · 2026Article
- Disrupted SR-Mitochondria Coupling Drives Ischemia-Reperfusion Vulnerability in the Middle-Aged Rat Heart.Biomedicines · 2026Article
271 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The organization and mutual interactions between endoplasmic reticulum (ER) and mitochondria modulate key aspects of cell pathophysiology. Several proteins have been suggested to be involved in keeping ER and mitochondria at a correct distance. Among them, in mammalian cells, mitofusin 2 (Mfn2), located on both the outer mitochondrial membrane and the ER surface, has been proposed to be a physical tether between the two organelles, forming homotypic interactions and heterocomplexes with its homolog Mfn1. Recently, this widely accepted model has been challenged using quantitative EM analysis. Using a multiplicity of morphological, biochemical, functional, and genetic approaches, we demonstrate that Mfn2 ablation increases the structural and functional ER-mitochondria coupling. In particular, we show that in different cell types Mfn2 ablation or silencing increases the close contacts between the two organelles and strengthens the efficacy of inositol trisphosphate (IP3)-induced Ca(2+) transfer from the ER to mitochondria, sensitizing cells to a mitochondrial Ca(2+) overload-dependent death. We also show that the previously reported discrepancy between electron and fluorescence microscopy data on ER-mitochondria proximity in Mfn2-ablated cells is only apparent. By using a different type of morphological analysis of fluorescent images that takes into account (and corrects for) the gross modifications in mitochondrial shape resulting from Mfn2 ablation, we demonstrate that an increased proximity between the organelles is also observed by confocal microscopy when Mfn2 levels are reduced. Based on these results, we propose a new model for ER-mitochondria juxtaposition in which Mfn2 works as a tethering antagonist preventing an excessive, potentially toxic, proximity between the two organelles.
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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.