ArticleAnnals of neurology2015
Hereditary spastic paraplegia-linked REEP1 modulates endoplasmic reticulum/mitochondria contacts.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 95 citations in OpenAlex.
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.Cell biology and toxicology · 2026Article
- An INF2-dependent actin-mediated step in inositol 1,4,5-trisphosphate receptor cluster formation and activity.Current biology : CB · 2026Article
- The expression significance and non-invasive detection of REEP6 and REEP5 in prostate cancer.BMC cancer · 2026Article
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
- Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.Frontiers in cellular neuroscience · 2025Review
- Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells.Journal of visualized experiments : JoVE · 2024Article
- Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER.The Journal of cell biology · 2024Article
- The interactions of subcellular organelles in pulmonary fibrosis induced by carbon black nanoparticles: a comprehensive review.Archives of toxicology · 2024Review
- Article
- Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular-Kidney-Metabolic Axis.Life (Basel, Switzerland) · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.SAGE open medicine · 2024Review
- REEP1 Preserves Motor Function in SOD1Neuroscience bulletin · 2023Article
- The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma.Biomedicines · 2023Article
- Converging Role for REEP1/SPG31 in Oxidative Stress.International journal of molecular sciences · 2023Article
- Synergistic mechanism between the endoplasmic reticulum and mitochondria and their crosstalk with other organelles.Cell death discovery · 2023Review
- TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia.Brain : a journal of neurology · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMutations in receptor expression enhancing protein 1 (REEP1) are associated with hereditary spastic paraplegias (HSPs). Although axonal degeneration is thought to be a predominant feature in HSP, the role of REEP1 mutations in degeneration is largely unknown. Previous studies have implicated a role for REEP1 in the endoplasmic reticulum (ER), whereas others localized REEP1 with mitochondria. We sought to resolve the cellular localization of REEP1 and further elucidate the pathobiology underlying REEP1 mutations in patients.
methodsA combination of cellular imaging and biochemical approaches was used to refine the cellular localization of REEP1. Next, Reep1 mutations associated with HSP were functionally tested in neuritic growth and degeneration assays using mouse cortical culture. Finally, a novel assay was developed and used with wild-type and mutant Reep1s to measure the interactions between the ER and mitochondria.
resultsWe found that REEP1 is present at the ER-mitochondria interface, and it contains subdomains for mitochondrial as well as ER localization. Knockdown of Reep1 and expression of pathological Reep1 mutations resulted in neuritic growth defects and degeneration. Finally, using our novel split-RLuc8 assay, we show that REEP1 facilitates ER-mitochondria interactions, a function diminished by disease-associated mutations.
interpretationOur data potentially reconcile the current conflicting reports regarding REEP1 being either an ER or a mitochondrial protein. Furthermore, our results connect, for the first time, the disrupted ER-mitochondria interactions to a failure in maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a new tool to identify potential drugs for multiple neurodegenerative diseases with ER-mitochondria interaction defects.
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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.