دورية أكاديمية
ALKBH7 mediates necrosis via rewiring of glyoxal metabolism
| العنوان: | ALKBH7 mediates necrosis via rewiring of glyoxal metabolism |
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| المؤلفون: | Chaitanya A Kulkarni, Sergiy M Nadtochiy, Leslie Kennedy, Jimmy Zhang, Sophea Chhim, Hanan Alwaseem, Elizabeth Murphy, Dragony Fu, Paul S Brookes |
| المصدر: | eLife, Vol 9 (2020) |
| بيانات النشر: | eLife Sciences Publications Ltd |
| سنة النشر: | 2020 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | mitochondria, ischemia, metabolism, glyoxalase, a-kg dioxygenase, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Alkb homolog 7 (ALKBH7) is a mitochondrial α-ketoglutarate dioxygenase required for DNA alkylation-induced necrosis, but its function and substrates remain unclear. Herein, we show ALKBH7 regulates dialdehyde metabolism, which impacts the cardiac response to ischemia-reperfusion (IR) injury. Using a multi-omics approach, we find no evidence ALKBH7 functions as a prolyl-hydroxylase, but we do find Alkbh7-/- mice have elevated glyoxalase I (GLO-1), a dialdehyde detoxifying enzyme. Metabolic pathways related to the glycolytic by-product methylglyoxal (MGO) are rewired in Alkbh7-/- mice, along with elevated levels of MGO protein adducts. Despite greater glycative stress, hearts from Alkbh7-/- mice are protected against IR injury, in a manner blocked by GLO-1 inhibition. Integrating these observations, we propose ALKBH7 regulates glyoxal metabolism, and that protection against necrosis and cardiac IR injury bought on by ALKBH7 deficiency originates from the signaling response to elevated MGO stress. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/58573Test; https://doaj.org/toc/2050-084XTest; e58573; https://doaj.org/article/0dc515db99d74ef0bd80e3abdb1bbe69Test |
| DOI: | 10.7554/eLife.58573 |
| الإتاحة: | https://doi.org/10.7554/eLife.58573Test https://doaj.org/article/0dc515db99d74ef0bd80e3abdb1bbe69Test |
| رقم الانضمام: | edsbas.70262396 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.58573 |