Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11
Some aquaporins (AQPs) can transport H2O2 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 H2O2 to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that genera...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001823 |
| _version_ | 1798042499447521280 |
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| author | Ilaria Sorrentino Mauro Galli Iria Medraño-Fernandez Roberto Sitia |
| author_facet | Ilaria Sorrentino Mauro Galli Iria Medraño-Fernandez Roberto Sitia |
| author_sort | Ilaria Sorrentino |
| collection | DOAJ |
| description | Some aquaporins (AQPs) can transport H2O2 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 H2O2 to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H2O2 during oxidative folding, causes a paradoxical increase in luminal H2O2 levels. The simultaneous AQP11 downregulation prevents this increase, implying that H2O2 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 H2O2 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 H2O2 from mitochondria to the ER via AQP11. |
| first_indexed | 2024-04-11T22:36:22Z |
| format | Article |
| id | doaj.art-0d5f2e0a92094bdcaccefe642543b7e4 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-11T22:36:22Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-0d5f2e0a92094bdcaccefe642543b7e42022-12-22T03:59:12ZengElsevierRedox Biology2213-23172022-09-0155102410Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11Ilaria Sorrentino0Mauro Galli1Iria Medraño-Fernandez2Roberto Sitia3Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, ItalyDepartment of Medical Biology, Medical University of Białystok, 15222, Białystok, PolandDepartment of Bioengineering and Aerospace Engineering, University Carlos III of Madrid, 28911, Madrid, Spain; Corresponding author.Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy; Corresponding author.Some aquaporins (AQPs) can transport H2O2 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 H2O2 to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H2O2 during oxidative folding, causes a paradoxical increase in luminal H2O2 levels. The simultaneous AQP11 downregulation prevents this increase, implying that H2O2 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 H2O2 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 H2O2 from mitochondria to the ER via AQP11.http://www.sciencedirect.com/science/article/pii/S2213231722001823Hydrogen peroxideRedox homeostasisInterorganellar crosstalk/ peroxiporinComplex IIIMitochondrial-associated membranes |
| spellingShingle | Ilaria Sorrentino Mauro Galli Iria Medraño-Fernandez Roberto Sitia Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 Redox Biology Hydrogen peroxide Redox homeostasis Interorganellar crosstalk/ peroxiporin Complex III Mitochondrial-associated membranes |
| title | Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 |
| title_full | Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 |
| title_fullStr | Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 |
| title_full_unstemmed | Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 |
| title_short | Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11 |
| title_sort | transfer of h2o2 from mitochondria to the endoplasmic reticulum via aquaporin 11 |
| topic | Hydrogen peroxide Redox homeostasis Interorganellar crosstalk/ peroxiporin Complex III Mitochondrial-associated membranes |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001823 |
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