Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players
Summary: Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscula...
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Format: | Article |
Language: | English |
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Elsevier
2023-04-01
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Series: | iScience |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223005254 |
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author | Alfonso Schiavi Eva Salveridou Vanessa Brinkmann Anjumara Shaik Ralph Menzel Sumana Kalyanasundaram Ståle Nygård Hilde Nilsen Natascia Ventura |
author_facet | Alfonso Schiavi Eva Salveridou Vanessa Brinkmann Anjumara Shaik Ralph Menzel Sumana Kalyanasundaram Ståle Nygård Hilde Nilsen Natascia Ventura |
author_sort | Alfonso Schiavi |
collection | DOAJ |
description | Summary: Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation. This is achieved by impacting on different key ferroptosis players and likely via gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel potential strategy to promote healthy aging. |
first_indexed | 2024-04-09T20:04:17Z |
format | Article |
id | doaj.art-718e9a6fdb4d42a78172e8de69e26027 |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-04-09T20:04:17Z |
publishDate | 2023-04-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
spelling | doaj.art-718e9a6fdb4d42a78172e8de69e260272023-04-02T06:14:08ZengElsevieriScience2589-00422023-04-01264106448Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis playersAlfonso Schiavi0Eva Salveridou1Vanessa Brinkmann2Anjumara Shaik3Ralph Menzel4Sumana Kalyanasundaram5Ståle Nygård6Hilde Nilsen7Natascia Ventura8Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, GermanyLeibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, GermanyLeibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, GermanyLeibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, GermanyHumboldt-Universität zu Berlin, Berlin, GermanyInstitute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, NorwayBioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, NorwayLeibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; Institute of Clinical Chemistry and Laboratory Diagnostic, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany; Corresponding authorSummary: Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation. This is achieved by impacting on different key ferroptosis players and likely via gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel potential strategy to promote healthy aging.http://www.sciencedirect.com/science/article/pii/S2589004223005254Cellular physiologyCellular neuroscienceCell biology |
spellingShingle | Alfonso Schiavi Eva Salveridou Vanessa Brinkmann Anjumara Shaik Ralph Menzel Sumana Kalyanasundaram Ståle Nygård Hilde Nilsen Natascia Ventura Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players iScience Cellular physiology Cellular neuroscience Cell biology |
title | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players |
title_full | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players |
title_fullStr | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players |
title_full_unstemmed | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players |
title_short | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players |
title_sort | mitochondria hormesis delays aging and associated diseases in caenorhabditis elegans impacting on key ferroptosis players |
topic | Cellular physiology Cellular neuroscience Cell biology |
url | http://www.sciencedirect.com/science/article/pii/S2589004223005254 |
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