A latest study by Dr. TIAN Ye’s group from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, revealed that mitochondrial stress coordinates chromatin remodeling and longevity through the phosphoregulation of Nucleosome Remodeling and Deacetylase (NuRD) complex component LIN-40 in Caenorhabditis elegans.
This finding for the first time clarifies the molecular mechanism by which the NuRD complex senses mitochondrial signals, providing a new perspective for understanding mitochondria-to-nucleus signaling and aging regulation. The related results were published in Science China Life Sciences on August 13, 2025 (DOI: 10.1007/s11427-025-2954-3).
Mitochondria are widely known as the energy center inside cells, but they can also serve as signaling hubs that influence aging, immunity, cell proliferation, and apoptosis. Intriguingly, previous studies in multiple model organisms, including Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus, have consistently shown that mild mitochondrial stress can promote organismal longevity. In C. elegans, such stress activates transcriptional responses in the nucleus, promoting the repairment of mitochondrial damage, reprogram metabolism, and stress adaptation.
Previous study by Tian’s Lab demonstrated that the NuRD complex, an epigenetic regulator of chromatin structure, plays a key role in mediating mitochondrial stress-induced longevity. However, how the NuRD complex senses mitochondrial signals remains unclear.
To sovle this puzzle, the research team purified the NuRD complex under mitochondrial stress conditions and conducted proteomic analysis. They identified stress-induced dephosphorylation at a specific site of LIN-40 (the C. elegans homolog of MTA), a core NuRD component. Genetic and biochemical analyses revealed that dephosphorylation of LIN-40/MTA promotes its interaction with the transcription factor DVE-1, which is essential for activating mitochondrial repair genes and chromatin remodeling, ultimately contributing to lifespan extension. Moreover, the study identified the kinase PMK-3 and phosphatase GSP-2 as key upstream regulators of LIN-40 phosphorylation.
This research reveals the functional and physiological significance of LIN-40/MTA dephosphorylation under mitochondrial stress, suggesting that novel mechanisms NuRD sense and response to mitochondrial stress to promote longevity. It provides an important molecular basis for in-depth understanding of mitochondria-to-nucleus signaling and aging regulation.
This work was supported by the National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, Youth Innovation Promotion Association CAS, and the New Cornerstone Science Foundation through the XPLORER PRIZE, etc.
The model of LIN-40 sensing mitochondrial stress via phosphorylation of T654 (Image by IGDB)
Contact:
Dr. TIAN Ye
Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences
Email: ytian@genetics.ac.cn
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