H2O2 transit through the mitochondrial intermembrane space promotes tumor cell growth in vitro and in vivo.
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| Title: | H |
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| Authors: | Sabharwal, Simran S.1,2, Dudley, V. Joseph1,2, Landwerlin, Charlène1,2, Schumacker, Paul T.1,2 p-schumacker@northwestern.edu |
| Source: | Journal of Biological Chemistry. May2023, Vol. 299 Issue 5, p1-15. 15p. |
| Subjects: | Cell growth, Tumor growth, Mitochondria, Cell proliferation, Electron transport, Oncogenes |
| Abstract: | Cancer cells experience increased levels of oxidant stress as a consequence of oncogene activation, nucleotide biosynthesis, and growth factor receptor signaling. Mitochondria contribute to this redox stress by generating reactive oxygen species (ROS) along the electron transport chain, which are released to the matrix and the intermembrane space (IMS). Assessing the contribution of mitochondrial ROS in cancer cells is technically difficult, as electron transport chain inhibitors can increase or decrease ROS generation, while they also block oxidative phosphorylation and ATP synthesis. Mitochondriatargeted antioxidant compounds can scavenge ROS in the matrix compartment but do not act on ROS released to the IMS. We assessed the importance of mitochondrial ROS for tumor cell proliferation, survival, and for tumor xenograft growth by stably expressing a hydrogen peroxide (H2O2) scavenger, peroxiredoxin-5, in the mitochondrial IMS (IMSPrdx5) in 143B osteosarcoma and HCT116 colorectal cancer cell lines. IMS-Prdx5 attenuates hypoxia-induced ROS signaling as assessed independently in cytosol and IMS, HIF-1a stabilization and activity, and cellular proliferation under normoxic and hypoxic culture conditions. It also suppressed tumor growth in vivo. Stable expression of nondegradable HIF- 1a only partially rescued proliferation in IMS-Prdx5- expressing cells, indicating that mitochondrial H2O2 signaling contributes to tumor cell proliferation and survival through HIF-dependent and HIF-independent mechanisms. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
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| Header | DbId: egs DbLabel: Engineering Source An: 163934485 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: H<subscript>2</subscript>O<subscript>2</subscript> transit through the mitochondrial intermembrane space promotes tumor cell growth in vitro and in vivo. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Sabharwal%2C+Simran+S%2E%22">Sabharwal, Simran S.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Dudley%2C+V%2E+Joseph%22">Dudley, V. Joseph</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Landwerlin%2C+Charlène%22">Landwerlin, Charlène</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Schumacker%2C+Paul+T%2E%22">Schumacker, Paul T.</searchLink><relatesTo>1,2</relatesTo><i> p-schumacker@northwestern.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. May2023, Vol. 299 Issue 5, p1-15. 15p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cell+growth%22">Cell growth</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+growth%22">Tumor growth</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondria%22">Mitochondria</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+proliferation%22">Cell proliferation</searchLink><br /><searchLink fieldCode="DE" term="%22Electron+transport%22">Electron transport</searchLink><br /><searchLink fieldCode="DE" term="%22Oncogenes%22">Oncogenes</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Cancer cells experience increased levels of oxidant stress as a consequence of oncogene activation, nucleotide biosynthesis, and growth factor receptor signaling. Mitochondria contribute to this redox stress by generating reactive oxygen species (ROS) along the electron transport chain, which are released to the matrix and the intermembrane space (IMS). Assessing the contribution of mitochondrial ROS in cancer cells is technically difficult, as electron transport chain inhibitors can increase or decrease ROS generation, while they also block oxidative phosphorylation and ATP synthesis. Mitochondriatargeted antioxidant compounds can scavenge ROS in the matrix compartment but do not act on ROS released to the IMS. We assessed the importance of mitochondrial ROS for tumor cell proliferation, survival, and for tumor xenograft growth by stably expressing a hydrogen peroxide (H2O2) scavenger, peroxiredoxin-5, in the mitochondrial IMS (IMSPrdx5) in 143B osteosarcoma and HCT116 colorectal cancer cell lines. IMS-Prdx5 attenuates hypoxia-induced ROS signaling as assessed independently in cytosol and IMS, HIF-1a stabilization and activity, and cellular proliferation under normoxic and hypoxic culture conditions. It also suppressed tumor growth in vivo. Stable expression of nondegradable HIF- 1a only partially rescued proliferation in IMS-Prdx5- expressing cells, indicating that mitochondrial H2O2 signaling contributes to tumor cell proliferation and survival through HIF-dependent and HIF-independent mechanisms. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jbc.2023.104624 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 15 StartPage: 1 Subjects: – SubjectFull: Cell growth Type: general – SubjectFull: Tumor growth Type: general – SubjectFull: Mitochondria Type: general – SubjectFull: Cell proliferation Type: general – SubjectFull: Electron transport Type: general – SubjectFull: Oncogenes Type: general Titles: – TitleFull: H2O2 transit through the mitochondrial intermembrane space promotes tumor cell growth in vitro and in vivo. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Sabharwal, Simran S. – PersonEntity: Name: NameFull: Dudley, V. Joseph – PersonEntity: Name: NameFull: Landwerlin, Charlène – PersonEntity: Name: NameFull: Schumacker, Paul T. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 299 – Type: issue Value: 5 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
