The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation

Cellular Mechanisms and Regulation of Quiescence

“…Indeed, the quiescent state is characterized by a substantial decrease in basal metabolic activity, energy production, and biosynthesis (Figure 4). Cellular ATP concentrations are significantly reduced during quiescence (Ho et al, 2017;Rodgers et al, 2014;Zhang et al, 2018), and some quiescent cell types decrease oxidative phosphorylation to instead rely on glycolysis as their primary metabolic pathway (Ho et al, 2017;Mohrin et al, 2018;Mu et al, 2020;Subramaniam et al, 2014;Zhang et al, 2018). Accordingly, both mitochondrial number and activity are reduced in quiescent cells (Figure 4), leading to decreased oxidative metabolism (Ho et al, 2017;Liang et al, 2020;Mohrin et al, 2018;Rodgers et al, 2014;Zhang et al, 2018).…”

“…The loss of mitophagy in hematopoiet-ic stem cells (HSCs) results in increased mitochondrial number, higher overall metabolic activity, and aberrant cell-cycle reentry (Ho et al, 2017). Reciprocally, the transition from quiescence to proliferation is accompanied by metabolic upregulation and an increase in mitochondrial biogenesis to meet the increased energy demands of proliferating cells (Ho et al, 2017;Mohrin et al, 2018;Mu et al, 2020). In addition to changes in energy production, activation from quiescence requires increased consumption of extracellular nutrients and anabolic biosynthesis to support cell growth.…”

Therapeutic hypothermia alleviates myocardial ischaemia–reperfusion injury by inhibiting inflammation and fibrosis via the mediation of the SIRT3/NLRP3 signalling pathway

“…SIRT3 can modify mitochondrial antioxidant superoxide dismutase 2 (SOD2) to reduce oxidative stress and prevent the development of cardiac hypertrophy. 7 SIRT3 can activate autophagy, and deacetylated forkhead box O 3α (FOXO3α) can activate the expression of a variety of autophagy genes, thereby protecting cells from apoptosis. SIRT3 induces the initiation and activation of the PINK1-Parkin autophagy pathway to inhibit cell death.…”

Emerging Evidence of the Significance of Thioredoxin-1 in Hematopoietic Stem Cell Aging

“…There is emerging evidence for an important mitochondrial checkpoint in the cell cycle regulation of quiescence. Several mechanistic studies have begun to describe an mTOR-LKB1-AMPK-dependent pathway regulation mitochondrial biogenesis, mitochondrial mass, and mitochondrial activity in the G 0 -to-G 1 cell cycle transition [ 80 , 175 , 176 ]. In the reverse order, it has been suggested that inadequate mitogenesis or a mitochondrial stress response (with contributing mitophagy) leads to a loss of HSC quiescence.…”