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OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress.

Alessandra Donato | Fiona K Ritchie | Lachlan Lu | Mehershad Wadia | Ramon Martinez-Marmol | Eva Kaulich | Kornraviya Sankorrakul | Hang Lu | Sean Coakley | Elizabeth J Coulson | Massimo A Hilliard
Nature communications | 2025

Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death is still very limited. Here, using Caenorhabditis elegans as a model system, combined with the optogenetic tool KillerRed to spatially and temporally control ROS generation, we identify a previously uncharacterized gene, oxidative stress protective 1 (osp-1), that protects C. elegans neurons from oxidative damage. Using rodent and human cell cultures, we also show that the protective effect of OSP-1 extends to mammalian cells. Moreover, we demonstrate that OSP-1 functions in a strictly cell-autonomous fashion, and that it localizes to the endoplasmic reticulum (ER) where it has an ER-remodeling function. Finally, we present evidence suggesting that OSP-1 may exert its neuroprotective function by influencing autophagy. Our results point to a potential role of OSP-1 in modulating autophagy, and suggest that overactivation of this cellular process could contribute to neuronal death triggered by oxidative damage.

Pubmed ID: 39746999

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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WormBase (tool)

RRID:SCR_003098

Central data repository for nematode biology including complete genomic sequence, gene predictions and orthology assignments from range of related nematodes.Data concerning genetics, genomics and biology of C. elegans and related nematodes. Derived from initial ACeDB database of C. elegans genetic and sequence information, WormBase includes genomic, anatomical and functional information of C. elegans, other Caenorhabditis species and other nematodes. Maintains public FTP site where researchers can find many commonly requested files and datasets, WormBase software and prepackaged databases.

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InterPro (tool)

RRID:SCR_006695

Service providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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FreeBayes (tool)

RRID:SCR_010761

A Bayesian genetic variant detector designed to find small polymorphisms, specifically SNPs, indels, MNPs, and complex events smaller than the length of a short-read sequencing alignment.

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SlideBook (tool)

RRID:SCR_014423

Digital microscopy software for research microscopy. It comes standard with drivers to control numerous instruments in and around the microscope. When online, data is acquired in a native-3D format over time, color and specimen locations in customizable experiment protocols. Data can be analyzed by a wide variety of tools for image processing including mathematical operations, statistics functions, analysis scripting and import to/export from MATLAB. Additional modules are available for special applications ranging from deconvolution to photomanipulation to multiphoton.

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TMHMM Server (tool)

RRID:SCR_014935

Web application for the prediction of transmembrane helices in proteins using Hidden Markov Models. FASTA formatted sequences can be uploaded via file or copy-paste, and output can be formatted as extensive with graphics, extensive without graphics, or one line per protein. Submissions are limited to 10,000 sequences and 4,000,000 amino acids - each sequence is limited to no more than 8,000 amino acids.

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Phobius (tool)

RRID:SCR_015643

Web application for combined transmembrane topology and signal peptide prediction. Used for whole genome annotation of signal peptides and transmembrane regions. Predictor is based on hidden Markov model (HMM) that models different sequence regions of signal peptide and different regions of transmembrane protein in series of interconnected states.

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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N2_(ancestral) (tool)

RRID:WB-STRAIN:WBStrain00000003

Caenorhabditis elegans with name C. elegans wild type (ancestral). from WB.

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HZ1688 (organism)

RRID:WB-STRAIN:WBStrain00008601

Caenorhabditis elegans with name atg-13(bp414) III. from WB.

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CB369 (organism)

RRID:WB-STRAIN:WBStrain00004155

Caenorhabditis elegans with name unc-51(e369) V. from WB.

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CZ10175 (organism)

RRID:WB-STRAIN:WBStrain00005421

Caenorhabditis elegans with name zdIs5 I. from WB.

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MT1522 (organism)

RRID:WB-STRAIN:WBStrain00026860

Caenorhabditis elegans with name ced-3(n717) IV. from WB.

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TG2435 (organism)

RRID:WB-STRAIN:WBStrain00034694

Caenorhabditis elegans with name vtIs1 V. from WB.

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CB1189 (organism)

RRID:WB-STRAIN:WBStrain00004264

Caenorhabditis elegans with name unc-51(e1189) V. from WB.

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CB1472 (organism)

RRID:WB-STRAIN:WBStrain00004340

Caenorhabditis elegans with name mec-6(e1342) I. from WB.

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HZ1684 (organism)

RRID:WB-STRAIN:WBStrain00008597

Caenorhabditis elegans with name atg-3(bp412) IV; him-5(e1490) V. from WB.

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