Serine synthesis controls mitochondrial biogenesis in macrophages

Author:

Wang Chuanlong12ORCID,Zhao Muyang1,Bin Peng1ORCID,Ye Yuyi1,Chen Qingyi1,Tang Zhiru2ORCID,Ren Wenkai1ORCID

Affiliation:

1. State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

2. Animal Nutrition and Bio-feed, College of Animal Science and Technology, Southwest University, Chongqing 400715, China.

Abstract

Mitochondrial dysfunction is the pivotal driving factor of multiple inflammatory diseases, and targeting mitochondrial biogenesis represents an efficacious approach to ameliorate such dysfunction in inflammatory diseases. Here, we demonstrated that phosphoglycerate dehydrogenase (PHGDH) deficiency promotes mitochondrial biogenesis in inflammatory macrophages. Mechanistically, PHGDH deficiency boosts mitochondrial reactive oxygen species (mtROS) by suppressing cytoplasmic glutathione synthesis. mtROS provokes hypoxia-inducible factor–1α signaling to direct nuclear specificity protein 1 and nuclear respiratory factor 1 transcription. Moreover, myeloid Phgdh deficiency reverses diet-induced obesity. Collectively, this study reveals that a mechanism involving de novo serine synthesis orchestrates mitochondrial biogenesis via mitochondrial-to-nuclear communication, and provides a potential therapeutic target for tackling inflammatory diseases and mitochondria-mediated diseases.

Publisher

American Association for the Advancement of Science (AAAS)

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