The mitochondrial carrier Citrin plays a role in regulating cellular energy during carcinogenesis
| Autor: | David Dimmock, Efrat Ben-Zeev, Ayelet Erez, Ziv Porat, Maxim Itkin, Sergey Malitsky, Inbal Geva, Shiran Rabinovich, Amir Bahat, Adam H. Buchaklian, Shani Agron, Smadar Levin-Zaidman, Lital Adler, Alon Silberman, Daniel Helbling |
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| Přispěvatelé: | G-INCPM, Weizmann Institute of Science [Rehovot, Israël] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis Carbohydrates Glutamic Acid Oxidative phosphorylation Mitochondrion medicine.disease_cause Mitochondrial Membrane Transport Proteins Oxidative Phosphorylation 03 medical and health sciences Cytosol 0302 clinical medicine Glutamates Neoplasms Genetics medicine Humans Glycolysis Molecular Targeted Therapy Molecular Biology Melanoma Germ-Line Mutation Citrullinemia [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics] biology Autophagy Mitochondrial carrier Cancer metabolism Mitochondria 3. Good health Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology Citrin 030220 oncology & carcinogenesis biology.protein NAD+ kinase |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2019, ⟨10.1038/s41388-019-0976-2⟩ |
| ISSN: | 0950-9232 1476-5594 |
| Popis: | International audience; Citrin, encoded by SLC25A13 gene, is an inner mitochondrial transporter that is part of the malate–aspartate shuttle, which regulates the NAD+/NADH ratio between the cytosol and mitochondria. Citrullinemia type II (CTLN-II) is an inherited disorder caused by germline mutations in SLC25A13, manifesting clinically in growth failure that can be alleviated by dietary restriction of carbohydrates. The association of citrin with glycolysis and NAD+/NADH ratio led us to hypothesize that it may play a role in carcinogenesis. Indeed, we find that citrin is upregulated in multiple cancer types and is essential for supplementing NAD+ for glycolysis and NADH for oxidative phosphorylation. Consequently, citrin deficiency associates with autophagy, whereas its overexpression in cancer cells increases energy production and cancer invasion. Furthermore, based on the human deleterious mutations in citrin, we found a potential inhibitor of citrin that restricts cancerous phenotypes in cells. Collectively, our findings suggest that targeting citrin may be of benefit for cancer therapy. |
| Databáze: | OpenAIRE |
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