ASI-RIM neuronal axis regulates systemic mitochondrial stress response via TGF-β signaling cascade
收藏中国科学院中国科学技术大学科学数据中心2026-01-10 收录
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资源简介：
Morphogens play a critical role in coordinating stress adaptation and aging
across tissues, yet their involvement in neuronal mitochondrial stress
responses and systemic effects remains unclear. In this study, we reveal that
the transforming growth factor beta (TGF-β) DAF-7 is pivotal in mediating the
intestinal mitochondrial unfolded protein response (UPRmt) in Caenorhabditis
elegans under neuronal mitochondrial stress. Two ASI sensory neurons produce DAF-7, which targets DAF-1/TGF-β receptors on RIM interneurons to
orchestrate a systemic UPRmt response. Remarkably, inducing mitochondrial
stress specifically in ASI neurons activates intestinal UPRmt, extends lifespan,
enhances pathogen resistance, and reduces both brood size and body fat
levels. Furthermore, dopamine positively regulates this UPRmt activation, while
GABA acts as a systemic suppressor. This study uncovers the intricate
mechanisms of systemic mitochondrial stress regulation, emphasizing the
vital role of TGF-β in metabolic adaptations that are crucial for organismal
fitness and aging during neuronal mitochondrial stress.
提供机构：
中国科学院遗传与发育生物学研究所
创建时间：
2025-04-07
