The Wnt signaling pathway mediates the molecular mechanism of the mitochondrial unfolded protein response between the nerves and the intestines.

Mitochondria are not only the center of cellular energy supply, but also one of the important organelles that regulate the aging process and affect neurodegenerative diseases.
when the mitochondrial function is impaired, the mitochondrial unfolded protein reaction (UPRmt) within the cell will be activated, so that the expression level of mitochondrial molecular companion, protease, metabolic-related genes, etc. will be raised, and the steady state balance of the mitochondrial will be rebuilt.
in multicellular bodies, different tissues (nerve cells-intestinal cells) also perceive and coordinate their mitochondrial unfolded protein reactions, eventually systematically regulating the body's overall metabolic level and affecting the aging process.
but how the organizations communicate and coordinate the regulation mechanism of the steady state of the mitochondria, it is not clear. On July 26,
, the Tian Yu Research Group of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, in collaboration with Andrew Dillin, a professor at the University of California, Berkeley, published an article on Cell entitled Mitochondrial unfolded the work of the protein is mediated-cell-non-autonomous by retromer-dependent Wnt signaling.
the study found that Wnt, an important factor in developmental regulation, is involved in medialation of the stress response of mitochondrial between nerve cells and intestinal cells.
and revealed that this cross-cell, trans-tissue regulatory mitochondrial stress response is achieved by relying on the Retromer complex, the Wnt signaling pathway, and the neurotransmitter pentasine. Using beautiful nematodes as a model, the
Tian's team established a system for the regulation of mitochondrial signaling between nerve cells and the intestines - polyQ40, an antidote protein expressed in the nerve cells of the online worm, which induces the mitochondrial unfolded protein reaction in the intestines.
genetic screening found that the Retromer complex was involved in regulating mitochondrial stress between nerve cells and the intestines. further research
found that the Retromer complex enabled this cross-cell trans-tissue mitochondrial signal transmission by recycling the Wnt secretion receptor MIG-14 and helping wnate eGL-20 secretion.
neurotransmitter pentasine (5-HT) is also involved in the Wnt-induced mitochondrial stress response between nerve cells and the intestines.
at the same time, direct expression of Wnt ligands in nerve cells and intestines not only activates mitochondrial stress response, but also prolongs the life of nematodes.
the results of this study, Wnt's new ability to regulate the steady state balance of mitochondrial and provide new therapeutic ideas for the treatment of neurodegenerative diseases and accompanying metabolic disorders. Zhang Xi, a ph.d. student in the
Tianxuan Research Group, Yu Xueyun, assistant researcher, and Chen Peng, a ph.D. student, are the co-authors of the thesis, and the other authors of the thesis include Liu Limeng, a postdoctoral fellow in Tian's research group, and Xinnan of the Andrew Dillin research group.
Tian and Andrew Dillin contributed to this paper.The paper's co-authors.
this research was supported by the Ministry of Science and Technology's key research and development program, "Protein Machines and Life Process Control", the Chinese Academy of Sciences pilot project, the National Natural Science Foundation of China, and the Youth Thousand Project.
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