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mTORC1-PGC1 axis regulates mitochondrial remodeling during reprogramming.
Wang, Lulu; Xu, Xueting; Jiang, Che; Ma, Gang; Huang, Yinghua; Zhang, Hui; Lai, Yiwei; Wang, Ming; Ahmed, Tanveer; Lin, Runxia; Guo, Wenjing; Luo, Zhiwei; Li, Wenjuan; Zhang, Meng; Ward, Carl; Qian, Minxian; Liu, Baohua; Esteban, Miguel A; Qin, Baoming.
Afiliação
  • Wang L; Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Xu X; Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Jiang C; Joint School of Life Sciences, GIBH and Guangzhou Medical University, China.
  • Ma G; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), China.
  • Huang Y; University of Chinese Academy of Sciences, Beijing, China.
  • Zhang H; Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Lai Y; Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Wang M; Joint School of Life Sciences, GIBH and Guangzhou Medical University, China.
  • Ahmed T; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), China.
  • Lin R; School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Guo W; Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Luo Z; Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Li W; Joint School of Life Sciences, GIBH and Guangzhou Medical University, China.
  • Zhang M; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), China.
  • Ward C; University of Chinese Academy of Sciences, Beijing, China.
  • Qian M; Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Liu B; Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
  • Esteban MA; Joint School of Life Sciences, GIBH and Guangzhou Medical University, China.
  • Qin B; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), China.
FEBS J ; 287(1): 108-121, 2020 01.
Article em En | MEDLINE | ID: mdl-31361392
ABSTRACT
Metabolic reprogramming, hallmarked by enhanced glycolysis and reduced mitochondrial activity, is a key event in the early phase of somatic cell reprogramming. Although extensive work has been conducted to identify the mechanisms of mitochondrial remodeling in reprogramming, many questions remain. In this regard, different laboratories have proposed a role in this process for either canonical (ATG5-dependent) autophagy-mediated mitochondrial degradation (mitophagy), noncanonical (ULK1-dependent, ATG5-independent) mitophagy, mitochondrial fission or reduced biogenesis due to mTORC1 suppression. Clarifying these discrepancies is important for providing a comprehensive picture of metabolic changes in reprogramming. Yet, the comparison among these studies is difficult because they use different reprogramming conditions and mitophagy detection/quantification methods. Here, we have systematically explored mitochondrial remodeling in reprogramming using different culture media and reprogramming factor cocktails, together with appropriate quantification methods and thorough statistical analysis. Our experiments show lack of evidence for mitophagy in mitochondrial remodeling in reprogramming, and further confirm that the suppression of the mTORC1-PGC1 pathway drives this process. Our work helps to clarify the complex interplay between metabolic changes and nutrient sensing pathways in reprogramming, which may also shed light on other contexts such as development, aging and cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Células-Tronco Embrionárias / Reprogramação Celular / Fibroblastos / Mitofagia / Alvo Mecanístico do Complexo 1 de Rapamicina / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Células-Tronco Embrionárias / Reprogramação Celular / Fibroblastos / Mitofagia / Alvo Mecanístico do Complexo 1 de Rapamicina / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article