Publication Date:
2015-03-21
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447312/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447312/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohrin, Mary -- Shin, Jiyung -- Liu, Yufei -- Brown, Katharine -- Luo, Hanzhi -- Xi, Yannan -- Haynes, Cole M -- Chen, Danica -- R01 AG040990/AG/NIA NIH HHS/ -- R01AG040061/AG/NIA NIH HHS/ -- T32 AG000266/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1374-7. doi: 10.1126/science.aaa2361.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; 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. ; Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. danicac@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792330" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Cell Aging
;
*Cell Cycle Checkpoints
;
Energy Metabolism
;
HEK293 Cells
;
Hematopoietic Stem Cells/metabolism/*physiology
;
Humans
;
Mice
;
Mice, Mutant Strains
;
Mitochondria/*metabolism
;
Mitochondrial Proteins/genetics/*metabolism
;
Nuclear Respiratory Factor 1/*metabolism
;
Protein Biosynthesis
;
Sirtuins/genetics/*metabolism
;
*Unfolded Protein Response
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
