دورية أكاديمية
The mitophagy receptor Bcl-2-like protein 13 stimulates adipogenesis by regulating mitochondrial oxidative phosphorylation and apoptosis in mice.
| العنوان: | The mitophagy receptor Bcl-2-like protein 13 stimulates adipogenesis by regulating mitochondrial oxidative phosphorylation and apoptosis in mice. |
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| المؤلفون: | Fujiwara M; Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074., Tian L; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074., Le PT; Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074., DeMambro VE; Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074., Becker KA; Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074., Rosen CJ; Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074.; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074., Guntur AR; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074 guntua@mmc.org. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2019 Aug 23; Vol. 294 (34), pp. 12683-12694. Date of Electronic Publication: 2019 Jul 02. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Apoptosis* , Mitophagy* , Oxidative Phosphorylation*, Adipogenesis/*genetics , Mitochondria/*metabolism , Proto-Oncogene Proteins c-bcl-2/*metabolism, Animals ; Cells, Cultured ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL |
| مستخلص: | Metabolic programming of bone marrow stromal cells (BMSCs) could influence the function of progenitor osteoblasts or adipocytes and hence determine skeletal phenotypes. Adipocytes predominantly utilize oxidative phosphorylation, whereas osteoblasts use glycolysis to meet ATP demand. Here, we compared progenitor differentiation from the marrow of two inbred mouse strains, C3H/HeJ (C3H) and C57BL6J (B6). These strains differ in both skeletal mass and bone marrow adiposity. We hypothesized that genetic regulation of metabolic programs controls skeletal stem cell fate. Our experiments identified Bcl-2-like protein 13 (Bcl2l13), a mitochondrial mitophagy receptor, as being critical for adipogenic differentiation. We also found that Bcl2l13 is differentially expressed in the two mouse strains, with C3H adipocyte progenitor differentiation being accompanied by a >2-fold increase in Bcl2l13 levels relative to B6 marrow adipocytes. Bcl2l13 expression also increased during adipogenic differentiation in mouse ear mesenchymal stem cells (eMSCs) and the murine preadipocyte cell line 3T3-L1. The higher Bcl2l13 expression correlated with increased mitochondrial fusion and biogenesis. Importantly, Bcl2l13 knockdown significantly impaired adipocyte differentiation in both 3T3-L1 cells and eMSCs. Mechanistically, Bcl2l13 knockdown reprogrammed cells to rely more on glycolysis to meet ATP demand in the face of impaired oxidative phosphorylation. Bcl2l13 knockdown in eMSCs increased mitophagy. Moreover, Bcl2l13 prevented apoptosis during adipogenesis. Our findings indicate that the mitochondrial receptor Bcl2l13 promotes adipogenesis by increasing oxidative phosphorylation, suppressing apoptosis, and providing mitochondrial quality control through mitophagy. We conclude that genetic programming of metabolism may be important for lineage determination and cell function within the bone marrow. (© 2019 Fujiwara et al.) |
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| معلومات مُعتمدة: | P30 GM106391 United States GM NIGMS NIH HHS; R24 DK092759 United States DK NIDDK NIH HHS; R03 AR068095 United States AR NIAMS NIH HHS; U54 GM115516 United States GM NIGMS NIH HHS; P20 GM121301 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: B-cell lymphoma 2 (Bcl-2) family; Bcl-2-like protein 13 (Bcl2l13); adipocyte; adipogenesis; apoptosis; bone marrow; energy metabolism; lineage determination; metabolic reprogramming; mitochondria; mitochondrial metabolism; mitophagy; oxidative phosphorylation |
| المشرفين على المادة: | 0 (BCL2L13 protein, mouse) 0 (Proto-Oncogene Proteins c-bcl-2) |
| تواريخ الأحداث: | Date Created: 20190704 Date Completed: 20200330 Latest Revision: 20210205 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC6709636 |
| DOI: | 10.1074/jbc.RA119.008630 |
| PMID: | 31266807 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
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| DOI: | 10.1074/jbc.RA119.008630 |