Figure 2. A metabolic checkpoint involving a UPR^mt via SIRT7 is required for stem cell maintainance.

Quiescent stem cells rely heavily on glycolysis. However, stem cell proliferation and differentiation is accompanied by increased mitochondrial biogenesis and a shift to oxidative phosphorylation (OxPhos). SIRT7 is a histone deacetylase transcriptionally induced during the mitochondrial stress associated with mitochondrial biogenesis in proliferating hematopoietic stem cells (HSCs). SIRT7 expression is induced during mitochondrial unfolded protein stress potentially to reduce the number of OxPhos proteins expressed so as to not further perturb a dysfunctional protein folding environment. In the context of HSCs, SIRT7 promotes a pristine mitochondrial proteostasis environment, which also limits mitochondrial biogenesis, cell proliferation and differentiation.