Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation
Summary: Mitochondrial dysfunction is a critical process in renal epithelial cells upon kidney injury. While its implication in kidney disease progression is established, the mechanisms modulating it remain unclear. Here, we describe the role of Lipocalin-2 (LCN2), a protein expressed in injured tub...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723010434 |
| _version_ | 1797736863256018944 |
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| author | Eloïse Marques Maraiza Alves Teixeira Clément Nguyen Fabiola Terzi Morgan Gallazzini |
| author_facet | Eloïse Marques Maraiza Alves Teixeira Clément Nguyen Fabiola Terzi Morgan Gallazzini |
| author_sort | Eloïse Marques |
| collection | DOAJ |
| description | Summary: Mitochondrial dysfunction is a critical process in renal epithelial cells upon kidney injury. While its implication in kidney disease progression is established, the mechanisms modulating it remain unclear. Here, we describe the role of Lipocalin-2 (LCN2), a protein expressed in injured tubular cells, in mitochondrial dysfunction. We show that LCN2 expression decreases mitochondrial mass and function and induces mitochondrial fragmentation. Importantly, while LCN2 expression favors DRP1 mitochondrial recruitment, DRP1 inhibition antagonizes LCN2’s effect on mitochondrial shape. Remarkably, LCN2 promotes mitochondrial fragmentation independently of its secretion or transport iron activity. Mechanistically, intracellular LCN2 expression increases mTOR activity, and rapamycin inhibits LCN2’s effect on mitochondrial shape. In vivo, Lcn2 gene inactivation prevents mTOR activation and mitochondrial length decrease observed upon ischemia-reperfusion-induced kidney injury (IRI) in Lcn2+/+ mice. Our data identify LCN2 as a key regulator of mitochondrial dynamics and further elucidate the mechanisms leading to mitochondrial dysfunction. |
| first_indexed | 2024-03-12T13:19:09Z |
| format | Article |
| id | doaj.art-1965e843d698442e91e0bdf7f60ba2dc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T13:19:09Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1965e843d698442e91e0bdf7f60ba2dc2023-08-26T04:43:14ZengElsevierCell Reports2211-12472023-09-01429113032Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activationEloïse Marques0Maraiza Alves Teixeira1Clément Nguyen2Fabiola Terzi3Morgan Gallazzini4Mechanisms and Therapeutic Strategies of Chronic Kidney Disease, INSERM U1151-CNRS UMR 8253, Université Paris Cité, Institut Necker Enfants Malades, 160 Rue de Vaugirard, 75015 Paris, FranceMechanisms and Therapeutic Strategies of Chronic Kidney Disease, INSERM U1151-CNRS UMR 8253, Université Paris Cité, Institut Necker Enfants Malades, 160 Rue de Vaugirard, 75015 Paris, FranceMechanisms and Therapeutic Strategies of Chronic Kidney Disease, INSERM U1151-CNRS UMR 8253, Université Paris Cité, Institut Necker Enfants Malades, 160 Rue de Vaugirard, 75015 Paris, FranceMechanisms and Therapeutic Strategies of Chronic Kidney Disease, INSERM U1151-CNRS UMR 8253, Université Paris Cité, Institut Necker Enfants Malades, 160 Rue de Vaugirard, 75015 Paris, FranceMechanisms and Therapeutic Strategies of Chronic Kidney Disease, INSERM U1151-CNRS UMR 8253, Université Paris Cité, Institut Necker Enfants Malades, 160 Rue de Vaugirard, 75015 Paris, France; Corresponding authorSummary: Mitochondrial dysfunction is a critical process in renal epithelial cells upon kidney injury. While its implication in kidney disease progression is established, the mechanisms modulating it remain unclear. Here, we describe the role of Lipocalin-2 (LCN2), a protein expressed in injured tubular cells, in mitochondrial dysfunction. We show that LCN2 expression decreases mitochondrial mass and function and induces mitochondrial fragmentation. Importantly, while LCN2 expression favors DRP1 mitochondrial recruitment, DRP1 inhibition antagonizes LCN2’s effect on mitochondrial shape. Remarkably, LCN2 promotes mitochondrial fragmentation independently of its secretion or transport iron activity. Mechanistically, intracellular LCN2 expression increases mTOR activity, and rapamycin inhibits LCN2’s effect on mitochondrial shape. In vivo, Lcn2 gene inactivation prevents mTOR activation and mitochondrial length decrease observed upon ischemia-reperfusion-induced kidney injury (IRI) in Lcn2+/+ mice. Our data identify LCN2 as a key regulator of mitochondrial dynamics and further elucidate the mechanisms leading to mitochondrial dysfunction.http://www.sciencedirect.com/science/article/pii/S2211124723010434CP: Metabolism |
| spellingShingle | Eloïse Marques Maraiza Alves Teixeira Clément Nguyen Fabiola Terzi Morgan Gallazzini Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation Cell Reports CP: Metabolism |
| title | Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation |
| title_full | Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation |
| title_fullStr | Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation |
| title_full_unstemmed | Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation |
| title_short | Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation |
| title_sort | lipocalin 2 induces mitochondrial dysfunction in renal tubular cells via mtor pathway activation |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723010434 |
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