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Manipulating mitochondrial electron flow enhances tumor immunogenicity.

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Title: Manipulating mitochondrial electron flow enhances tumor immunogenicity.
Authors: Mangalhara, Kailash Chandra, Varanasi, Siva Karthik, Johnson, Melissa A., Burns, Mannix J., Rojas, Gladys R., Esparza Moltó, Pau B., Sainz, Alva G., Tadepalle, Nimesha, Abbott, Keene L., Mendiratta, Gaurav, Dan Chen, Farsakoglu, Yagmur, Tenzin Kunchok, Hoffmann, Filipe Araujo, Parisi, Bianca, Rincon, Mercedes, Vander Heiden, Matthew G., Bosenberg, Marcus, Hargreaves, Diana C., Kaech, Susan M.
Source: Science (pre-March 2025). 9/22/2023, Vol. 381 Issue 6664, p1316-1323. 8p. 5 Diagrams.
Subjects: Immune response, Electron transport, Mitochondria, Electrons, Tumor growth, T cell receptors, Amyloid beta-protein precursor, Photosystems
Abstract: Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell–mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex–antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially throughCI, provides proof of conceptof ETCrewiringtoachieve antitumor responses withoutsideeffects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science 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: Psychology and Behavioral Sciences Collection
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PubTypeId: academicJournal
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  Data: Manipulating mitochondrial electron flow enhances tumor immunogenicity.
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  Data: <searchLink fieldCode="AR" term="%22Mangalhara%2C+Kailash+Chandra%22">Mangalhara, Kailash Chandra</searchLink><br /><searchLink fieldCode="AR" term="%22Varanasi%2C+Siva+Karthik%22">Varanasi, Siva Karthik</searchLink><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Melissa+A%2E%22">Johnson, Melissa A.</searchLink><br /><searchLink fieldCode="AR" term="%22Burns%2C+Mannix+J%2E%22">Burns, Mannix J.</searchLink><br /><searchLink fieldCode="AR" term="%22Rojas%2C+Gladys+R%2E%22">Rojas, Gladys R.</searchLink><br /><searchLink fieldCode="AR" term="%22Esparza+Moltó%2C+Pau+B%2E%22">Esparza Moltó, Pau B.</searchLink><br /><searchLink fieldCode="AR" term="%22Sainz%2C+Alva+G%2E%22">Sainz, Alva G.</searchLink><br /><searchLink fieldCode="AR" term="%22Tadepalle%2C+Nimesha%22">Tadepalle, Nimesha</searchLink><br /><searchLink fieldCode="AR" term="%22Abbott%2C+Keene+L%2E%22">Abbott, Keene L.</searchLink><br /><searchLink fieldCode="AR" term="%22Mendiratta%2C+Gaurav%22">Mendiratta, Gaurav</searchLink><br /><searchLink fieldCode="AR" term="%22Dan+Chen%22">Dan Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Farsakoglu%2C+Yagmur%22">Farsakoglu, Yagmur</searchLink><br /><searchLink fieldCode="AR" term="%22Tenzin+Kunchok%22">Tenzin Kunchok</searchLink><br /><searchLink fieldCode="AR" term="%22Hoffmann%2C+Filipe+Araujo%22">Hoffmann, Filipe Araujo</searchLink><br /><searchLink fieldCode="AR" term="%22Parisi%2C+Bianca%22">Parisi, Bianca</searchLink><br /><searchLink fieldCode="AR" term="%22Rincon%2C+Mercedes%22">Rincon, Mercedes</searchLink><br /><searchLink fieldCode="AR" term="%22Vander+Heiden%2C+Matthew+G%2E%22">Vander Heiden, Matthew G.</searchLink><br /><searchLink fieldCode="AR" term="%22Bosenberg%2C+Marcus%22">Bosenberg, Marcus</searchLink><br /><searchLink fieldCode="AR" term="%22Hargreaves%2C+Diana+C%2E%22">Hargreaves, Diana C.</searchLink><br /><searchLink fieldCode="AR" term="%22Kaech%2C+Susan+M%2E%22">Kaech, Susan M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 9/22/2023, Vol. 381 Issue 6664, p1316-1323. 8p. 5 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Immune+response%22">Immune response</searchLink><br /><searchLink fieldCode="DE" term="%22Electron+transport%22">Electron transport</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondria%22">Mitochondria</searchLink><br /><searchLink fieldCode="DE" term="%22Electrons%22">Electrons</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+growth%22">Tumor growth</searchLink><br /><searchLink fieldCode="DE" term="%22T+cell+receptors%22">T cell receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Amyloid+beta-protein+precursor%22">Amyloid beta-protein precursor</searchLink><br /><searchLink fieldCode="DE" term="%22Photosystems%22">Photosystems</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell–mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex–antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially throughCI, provides proof of conceptof ETCrewiringtoachieve antitumor responses withoutsideeffects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion. [ABSTRACT FROM AUTHOR]
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  Label:
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science 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.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=172262913
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      – Type: doi
        Value: 10.1126/science.abq1053
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      – Code: eng
        Text: English
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        PageCount: 8
        StartPage: 1316
    Subjects:
      – SubjectFull: Immune response
        Type: general
      – SubjectFull: Electron transport
        Type: general
      – SubjectFull: Mitochondria
        Type: general
      – SubjectFull: Electrons
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      – SubjectFull: Tumor growth
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      – SubjectFull: T cell receptors
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      – SubjectFull: Amyloid beta-protein precursor
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      – SubjectFull: Photosystems
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              Text: 9/22/2023
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