A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging

• DOI: 10.1126/science.aaa2361
• Publication Date: 2015-03-19T18:11:38Z
• Authors: Mary Mohrin; Jiyung Shin; Yufei Liu; Katharine Brown; Hanzhi Luo; Yannan Xi; Cole M. Haynes; Danica Chen
• Keywords: Proteostasis; Hematopoietic stem cell; NRF1; Regenerative Medicine

Deterioration of adult stem cells accounts for much aging-associated compromised tissue maintenance. How maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch the mitochondrial unfolded protein response (UPR(mt)), which is mediated by interplay SIRT7 and NRF1 coupled to cellular energy metabolism proliferation. inactivation caused reduced quiescence, increased folding stress (PFS(mt)), regenerative capacity hematopoietic (HSCs). expression was in aged HSCs, up-regulation improved HSCs. These findings define deregulation UPR(mt)-mediated checkpoint as reversible contributing factor HSC aging.