ArticleJournal of cellular and molecular medicine2016
Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 162 citations in OpenAlex.
- Mitochondria-endoplasmic reticulum-lipid droplet crosstalk in lipid metabolic reprogramming in type 2 diabetes mellitus.Journal of lipid research · 2026Review
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction.Cell discovery · 2026Article
- STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria.The EMBO journal · 2026Article
- Mitochondria-associated membranes (MAMs): molecular organization, cellular functions, and their role in health and disease.FEBS open bio · 2026Review
- Salivary mitofusin levels in periodontal disease: a cross-sectional case-control study.BMC oral health · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Sarcoplasmic reticulum-mitochondria microdomains: hugging and kissing in the heart.American journal of physiology. Cell physiology · 2025Review
- The impact of ERCell death & disease · 2025Article
- New insights into the 17β-hydroxysteroid dehydrogenase type 10 and amyloid-β 42 derived cytotoxicity relevant to Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Visual Analysis of Research Hotspots and Trends on Mitochondria-Associated Membranes in the Past 20 Years-Focused on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease and future strategies for targeted therapy.European journal of medical research · 2025Review
- Shape Matters: The Utility and Analysis of Altered Yeast Mitochondrial Morphology in Health, Disease, and Biotechnology.International journal of molecular sciences · 2025Review
- Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.Frontiers in neuroscience · 2025Review
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- CRISPR/Cas9-mediated knock-in cells of the late-onset Alzheimer's disease-risk variant, SHARPIN G186R, reveal reduced NF-κB pathway and accelerated Aβ secretion.Journal of human genetics · 2024Article
- ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome.The Journal of biological chemistry · 2024Article
- The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria.EMBO reports · 2024Article
- Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Membrane contact site detection (MCS-DETECT) reveals dual control of rough mitochondria-ER contacts.The Journal of cell biology · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondria are physically and biochemically in contact with other organelles including the endoplasmic reticulum (ER). Such contacts are formed between mitochondria-associated ER membranes (MAM), specialized subregions of ER, and the outer mitochondrial membrane (OMM). We have previously shown increased expression of MAM-associated proteins and enhanced ER to mitochondria Ca(2+) transfer from ER to mitochondria in Alzheimer's disease (AD) and amyloid β-peptide (Aβ)-related neuronal models. Here, we report that siRNA knockdown of mitofusin-2 (Mfn2), a protein that is involved in the tethering of ER and mitochondria, leads to increased contact between the two organelles. Cells depleted in Mfn2 showed increased Ca(2+) transfer from ER to mitchondria and longer stretches of ER forming contacts with OMM. Interestingly, increased contact resulted in decreased concentrations of intra- and extracellular Aβ40 and Aβ42 . Analysis of γ-secretase protein expression, maturation and activity revealed that the low Aβ concentrations were a result of impaired γ-secretase complex function. Amyloid-β precursor protein (APP), β-site APP-cleaving enzyme 1 and neprilysin expression as well as neprilysin activity were not affected by Mfn2 siRNA treatment. In summary, our data shows that modulation of ER-mitochondria contact affects γ-secretase activity and Aβ generation. Increased ER-mitochondria contact results in lower γ-secretase activity suggesting a new mechanism by which Aβ generation can be controlled.
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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.