Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice
<p dir="ltr">Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription f...
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| مؤلفون آخرون: | , , , , , , , , , , , , , |
| منشور في: |
2023
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| _version_ | 1864513507569958912 |
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| author | Tomas Venit (17248420) |
| author2 | Oscar Sapkota (19459579) Wael Said Abdrabou (19459582) Palanikumar Loganathan (19459585) Renu Pasricha (2680573) Syed Raza Mahmood (15239737) Nadine Hosny El Said (19459588) Shimaa Sherif (12862990) Sneha Thomas (14424838) Salah Abdelrazig (4054825) Shady Amin (19459591) Davide Bedognetti (2632474) Youssef Idaghdour (44750) Mazin Magzoub (4583662) Piergiorgio Percipalle (393101) |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Tomas Venit (17248420) Oscar Sapkota (19459579) Wael Said Abdrabou (19459582) Palanikumar Loganathan (19459585) Renu Pasricha (2680573) Syed Raza Mahmood (15239737) Nadine Hosny El Said (19459588) Shimaa Sherif (12862990) Sneha Thomas (14424838) Salah Abdelrazig (4054825) Shady Amin (19459591) Davide Bedognetti (2632474) Youssef Idaghdour (44750) Mazin Magzoub (4583662) Piergiorgio Percipalle (393101) |
| author_role | author |
| dc.creator.none.fl_str_mv | Tomas Venit (17248420) Oscar Sapkota (19459579) Wael Said Abdrabou (19459582) Palanikumar Loganathan (19459585) Renu Pasricha (2680573) Syed Raza Mahmood (15239737) Nadine Hosny El Said (19459588) Shimaa Sherif (12862990) Sneha Thomas (14424838) Salah Abdelrazig (4054825) Shady Amin (19459591) Davide Bedognetti (2632474) Youssef Idaghdour (44750) Mazin Magzoub (4583662) Piergiorgio Percipalle (393101) |
| dc.date.none.fl_str_mv | 2023-10-10T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41467-023-42093-w |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Positive_regulation_of_oxidative_phosphorylation_by_nuclear_myosin_1_protects_cells_from_metabolic_reprogramming_and_tumorigenesis_in_mice/26798155 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Metabolic Reprogramming Tumorigenesis Nuclear Myosin 1 (NM1) Cellular Metabolism Aerobic Glycolysis Warburg Effect Cancer Metabolism Metabolomics |
| dc.title.none.fl_str_mv | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41467-023-42093-w" target="_blank">https://dx.doi.org/10.1038/s41467-023-42093-w</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b8b88a501ff701fd8f579db86535a1f2 |
| identifier_str_mv | 10.1038/s41467-023-42093-w |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26798155 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in miceTomas Venit (17248420)Oscar Sapkota (19459579)Wael Said Abdrabou (19459582)Palanikumar Loganathan (19459585)Renu Pasricha (2680573)Syed Raza Mahmood (15239737)Nadine Hosny El Said (19459588)Shimaa Sherif (12862990)Sneha Thomas (14424838)Salah Abdelrazig (4054825)Shady Amin (19459591)Davide Bedognetti (2632474)Youssef Idaghdour (44750)Mazin Magzoub (4583662)Piergiorgio Percipalle (393101)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsOncology and carcinogenesisMetabolic ReprogrammingTumorigenesisNuclear Myosin 1 (NM1)Cellular MetabolismAerobic GlycolysisWarburg EffectCancer MetabolismMetabolomics<p dir="ltr">Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41467-023-42093-w" target="_blank">https://dx.doi.org/10.1038/s41467-023-42093-w</a></p>2023-10-10T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41467-023-42093-whttps://figshare.com/articles/journal_contribution/Positive_regulation_of_oxidative_phosphorylation_by_nuclear_myosin_1_protects_cells_from_metabolic_reprogramming_and_tumorigenesis_in_mice/26798155CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/267981552023-10-10T09:00:00Z |
| spellingShingle | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice Tomas Venit (17248420) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Metabolic Reprogramming Tumorigenesis Nuclear Myosin 1 (NM1) Cellular Metabolism Aerobic Glycolysis Warburg Effect Cancer Metabolism Metabolomics |
| status_str | publishedVersion |
| title | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| title_full | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| title_fullStr | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| title_full_unstemmed | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| title_short | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| title_sort | Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis Metabolic Reprogramming Tumorigenesis Nuclear Myosin 1 (NM1) Cellular Metabolism Aerobic Glycolysis Warburg Effect Cancer Metabolism Metabolomics |