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Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11

Some aquaporins (AQPs) can transport H(2)O(2) across membranes, allowing redox signals to proceed in and between cells. Unlike other peroxiporins, human AQP11 is an endoplasmic reticulum (ER)-resident that can conduit H(2)O(2) to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme tha...

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Autores principales: Sorrentino, Ilaria, Galli, Mauro, Medraño-Fernandez, Iria, Sitia, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304643/
https://www.ncbi.nlm.nih.gov/pubmed/35863264
http://dx.doi.org/10.1016/j.redox.2022.102410
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author Sorrentino, Ilaria
Galli, Mauro
Medraño-Fernandez, Iria
Sitia, Roberto
author_facet Sorrentino, Ilaria
Galli, Mauro
Medraño-Fernandez, Iria
Sitia, Roberto
author_sort Sorrentino, Ilaria
collection PubMed
description Some aquaporins (AQPs) can transport H(2)O(2) across membranes, allowing redox signals to proceed in and between cells. Unlike other peroxiporins, human AQP11 is an endoplasmic reticulum (ER)-resident that can conduit H(2)O(2) to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H(2)O(2) during oxidative folding, causes a paradoxical increase in luminal H(2)O(2) levels. The simultaneous AQP11 downregulation prevents this increase, implying that H(2)O(2) reaches the ER from an external source(s). Pharmacological inhibition of the electron transport chain reveals that Ero1α downregulation activates superoxide production by complex III. In the intermembrane space, superoxide dismutase 1 generates H(2)O(2) that enters the ER channeled by AQP11. Meanwhile, the number of ER-mitochondria contact sites increases as well, irrespective of AQP11 expression. Taken together, our findings identify a novel interorganellar redox response that is activated upon Ero1α downregulation and transfers H(2)O(2) from mitochondria to the ER via AQP11.
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spelling pubmed-93046432022-07-23 Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11 Sorrentino, Ilaria Galli, Mauro Medraño-Fernandez, Iria Sitia, Roberto Redox Biol Research Paper Some aquaporins (AQPs) can transport H(2)O(2) across membranes, allowing redox signals to proceed in and between cells. Unlike other peroxiporins, human AQP11 is an endoplasmic reticulum (ER)-resident that can conduit H(2)O(2) to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H(2)O(2) during oxidative folding, causes a paradoxical increase in luminal H(2)O(2) levels. The simultaneous AQP11 downregulation prevents this increase, implying that H(2)O(2) reaches the ER from an external source(s). Pharmacological inhibition of the electron transport chain reveals that Ero1α downregulation activates superoxide production by complex III. In the intermembrane space, superoxide dismutase 1 generates H(2)O(2) that enters the ER channeled by AQP11. Meanwhile, the number of ER-mitochondria contact sites increases as well, irrespective of AQP11 expression. Taken together, our findings identify a novel interorganellar redox response that is activated upon Ero1α downregulation and transfers H(2)O(2) from mitochondria to the ER via AQP11. Elsevier 2022-07-16 /pmc/articles/PMC9304643/ /pubmed/35863264 http://dx.doi.org/10.1016/j.redox.2022.102410 Text en © 2022 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Sorrentino, Ilaria
Galli, Mauro
Medraño-Fernandez, Iria
Sitia, Roberto
Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title_full Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title_fullStr Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title_full_unstemmed Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title_short Transfer of H(2)O(2) from Mitochondria to the endoplasmic reticulum via Aquaporin-11
title_sort transfer of h(2)o(2) from mitochondria to the endoplasmic reticulum via aquaporin-11
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304643/
https://www.ncbi.nlm.nih.gov/pubmed/35863264
http://dx.doi.org/10.1016/j.redox.2022.102410
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