Identification of FAM173B as a protein methyltransferase promoting chronic pain

Willemen, Hanneke L. D. M.; Kavelaars, Annemieke; Prado, Judith; Maas, Mirjam; Versteeg, Sabine; Nellissen, Lara J. J.; Tromp, Jeshua; Gonzalez Cano, Rafael; Zhou, Wenjun; Jakobsson, Magnus E.; Malecki, Jedrzej; Posthuma, George; Habib, Abdella M.; Heijnen

Publicación: PLOS BIOLOGY
VL / 16 - BP / - EP /
Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity. FAM173B methyltransferase activity in sensory neurons hyperpolarized mitochondria and promoted macrophage/microglia activation through a reactive oxygen species-dependent pathway. In summary, we uncover a role for methyltransferase activity of FAM173B in the neurobiology of pain. These results also highlight FAM173B methyltransferase activity as a potential therapeutic target to treat debilitating chronic pain conditions.

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Gold DOAJ, Green published