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mTORC 1‐ PGC 1 axis regulates mitochondrial remodeling during reprogramming
Author(s) -
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
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15024
Subject(s) - mitophagy , reprogramming , microbiology and biotechnology , autophagy , mitochondrial biogenesis , mitochondrion , biology , cell , biochemistry , apoptosis
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 ( ATG 5‐dependent) autophagy‐mediated mitochondrial degradation (mitophagy), noncanonical ( ULK 1‐dependent, ATG 5‐independent) mitophagy, mitochondrial fission or reduced biogenesis due to mTORC 1 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 mTORC 1‐ PGC 1 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.