ArticleThe Journal of biological chemistry2012
Expression of a truncated form of the endoplasmic reticulum chaperone protein, σ1 receptor, promotes mitochondrial energy depletion and apoptosis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Investigation of the modulatory effects of fabomotizole and/or sertraline on cisplatin nephrotoxicity via in vivo and in vitro approaches: insights into the role of Sig-1R/ERK1/2 signaling in regulating mitochondrial dynamics and apoptotic cellular death.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- SIGMAR1 targets AMPK/ULK1 pathway to inhibit SH-SY5Y cell apoptosis by regulating endoplasmic reticulum stress and autophagy.Functional & integrative genomics · 2024Article
- Key genes expressed in mitochondria‑endoplasmic reticulum contact sites in cancer (Review).Oncology reports · 2023Review
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
- Sigma‑1 receptor overexpression promotes proliferation and ameliorates cell apoptosis in β‑cells.Molecular medicine reports · 2022Article
- Sigma receptor knockdown augments dysfunction and apoptosis of beta cells induced by palmitate.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine.Behavioural neurology · 2021Article
- Wildtype σ1 receptor and the receptor agonist improve ALS-associated mutation-induced insolubility and toxicity.The Journal of biological chemistry · 2020Article
- Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Prospective Roles in Kidney Disease.Oxidative medicine and cellular longevity · 2020Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor.Neurobiology of disease · 2019Article
- Choline Is an Intracellular Messenger Linking Extracellular Stimuli to IPCell reports · 2019Article
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
- SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome.International journal of molecular sciences · 2018Article
- Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases.Journal of biomedical science · 2017Review
- Isolation and characterization of alternatively spliced variants of the mouse sigma1 receptor gene, Sigmar1.PloS one · 2017Article
- Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection.Advances in experimental medicine and biology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The σ1 receptor (σ(1)R) regulates endoplasmic reticulum (ER)/mitochondrial interorganellar Ca(2+) mobilization through the inositol 1,4,5-trisphosphate receptor (IP(3)R). Here, we observed that expression of a novel splice variant of σ(1)R, termed short form σ(1)R (σ(1)SR), has a detrimental effect on mitochondrial energy production and cell survival. σ(1)SR mRNA lacks 47 ribonucleotides encoding exon 2, resulting in a frameshift and formation of a truncated receptor. σ(1)SR localizes primarily in the ER at perinuclear regions and forms a complex with σ(1)R but not with IP(3)R in the mitochondrion-associated ER membrane. Overexpression of both σ(1)R and the truncated isoform promotes mitochondrial elongation with increased ER mitochondrial contact surface. σ(1)R overexpression increases the efficiency of mitochondrial Ca(2+) uptake in response to IP(3)R-driven stimuli, whereas σ(1)SR overexpression reduces it. Most importantly, σ(1)R promotes ATP production via increased mitochondrial Ca(2+) uptake, promoting cell survival in the presence of ER stress. By contrast, σ(1)SR suppresses ATP production following ER stress, enhancing cell death. Taken together, the newly identified σ(1)SR isoform interferes with σ(1)R function relevant to mitochondrial energy production under ER stress conditions, promoting cellular apoptosis.
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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.