Serine synthesis controls mitochondrial biogenesis in macrophages.
Sci Adv
; 10(20): eadn2867, 2024 May 17.
Article
en En
| MEDLINE
| ID: mdl-38758794
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina
/
Biogénesis de Organelos
/
Especies Reactivas de Oxígeno
/
Fosfoglicerato-Deshidrogenasa
/
Macrófagos
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2024
Tipo del documento:
Article
País de afiliación:
China