粒体自噬
细胞生物学
线粒体分裂
线粒体
神经生长因子
生物
糖酵解
化学
神经科学
生物化学
新陈代谢
细胞凋亡
受体
自噬
作者
Ilaria Goglia,Ewelina Węglarz‐Tomczak,C. Gioia,Yanhua Liu,Assunta Virtuoso,Marcella Bonanomi,Daniela Gaglio,Noemi Salmistraro,Ciro De Luca,Michèle Papa,Lilia Alberghina,Hans V. Westerhoff,Anna Maria Colangelo
出处
期刊:FEBS Journal
[Wiley]
日期:2024-02-16
卷期号:291 (13): 2811-2835
被引量:1
摘要
Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time-lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration. Then, we reconstructed the dynamic fusion-fission-mitophagy cycling of mitochondria in a computer model, integrating these processes into a single network mechanism. Both the computational model and the simulations are able to reproduce the proposed mechanism in terms of mitochondrial dynamics, levels of reactive oxygen species (ROS), mitophagy, and mitochondrial quality, thus providing a computational tool for the interpretation of the experimental data and for future studies aiming to detail further the action of NGF on mitochondrial processes. We also show that changes in these mitochondrial processes are intertwined with a metabolic function of NGF in differentiation: NGF directs a profound metabolic rearrangement involving glycolysis, TCA cycle, and the pentose phosphate pathway, altering the redox balance. This metabolic rewiring may ensure: (a) supply of both energy and building blocks for the anabolic processes needed for morphological reorganization, as well as (b) redox homeostasis.
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