title: Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging.
abstract: Deterioration of adult stem cells accounts for much of aging-associated compromised tissue maintenance. How stem cells maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. SIRT7 inactivation caused reduced quiescence, increased mitochondrial protein folding stress (PFS(mt)), and compromised regenerative capacity of hematopoietic stem cells (HSCs). SIRT7 expression was reduced in aged HSCs, and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. These findings define the deregulation of a UPR(mt)-mediated metabolic checkpoint as a reversible contributing factor for HSC aging.
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Mary
authors: M
authors: Mohrin
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Jiyung
authors: J
authors: Shin
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Yufei
authors: Y
authors: Liu
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Katharine
authors: K
authors: Brown
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Hanzhi
authors: H
authors: Luo
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Yannan
authors: Y
authors: Xi
authors: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Biochemistry, Cell and Molecular Biology Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USA.
authors: Cole M
authors: CM
authors: Haynes
authors: Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. danicac@berkeley.edu.
authors: Danica
authors: D
authors: Chen
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D016922:Cellular Senescence; D004734:Energy Metabolism; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism*; D014176:Protein Biosynthesis; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D024101:Mitochondrial Proteins; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C510661:SIRT7 protein, human; D037761:Sirtuins