Mitochondrial pyruvate carriers control airway basal progenitor cell function through glycolytic-epigenetic reprogramming
Yawen Li, et al.
Cell Stem Cell, 2024
Basal cells are essential progenitors that preserve tracheal epithelium integrity. Our research highlights mitochondrial pyruvate carriers (MPCs) as key metabolic checkpoints that govern basal cell fate. Blocking MPC activity promotes the long-term expansion of basal cells from both mice and humans. In mice, genetic deletion of Mpc2 causes abnormal proliferation, a reduction in ciliated cells under normal conditions, delayed epithelial repair, and an accumulation of transitional cell states after injury.Further analysis reveals that MPC2 connects glycolysis to ATP citrate lyase -dependent production of cytosolic acetyl-coenzyme A, a critical factor for the epigenetic regulation of differentiation-related genes. Restoring this metabolic-epigenetic balance partially reverses abnormalities caused by Yes-associated protein dysfunction in basal cells. Notably, exogenous citrate stimulates basal cell differentiation in samples from chronic obstructive pulmonary disease patients.This study not only uncovers the crucial role of pyruvate metabolism in basal cell fate determination but also proposes targeting the pyruvate-citrate pathway as a potential therapeutic strategy to correct basal cell dysfunction in lung diseases.DOI: 10.1016/j.stem.2024.09.015
Melatonin treatment increases skin microbiota-derived propionic acid to alleviate atopic dermatitis![]()
Lan Yang,et al.
J Allergy Clin Immunol，2024.
Atopic dermatitis (AD) is a common chronic skin disease with limited effective treatments. It is known for its itchy and inflamed skin, and current therapies mainly alleviate symptoms without addressing the underlying causes. There is a growing interest in the role of skin microbiota in AD, and melatonin, a hormone with anti-inflammatory properties, has been studied for its potential to modulate the skin microbiota and alleviate AD symptoms.This study investigated how melatonin treatment affects skin microbiota composition and function in a mouse model of AD. The researchers used 16S-rRNA sequencing, metabolomics, and transcriptomic sequencing to analyze changes in skin microbiota after melatonin treatment. They found that melatonin increased the levels of skin microbiota-derived short-chain fatty acids, particularly propionic acid, which was linked to the inhibition of fatty acid-binding protein 5 (FABP5) expression through the G-protein-coupled receptor 43 (GPR43).They conclude that melatonin treatment can alleviate AD symptoms by modulating the skin microbiota and its metabolites, specifically through the propionic acid/GPR43/FABP5 axis. This finding suggests a new therapeutic approach for AD, targeting the skin microbiota and its interactions with melatonin, which could lead to more effective treatments for the condition.DOI: 10.1016/j.jaci.2024.11.019
Editor & Reviewer: Congci Yu
