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Review
. 2020 Jun:188:111254.
doi: 10.1016/j.mad.2020.111254. Epub 2020 Apr 25.

The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation

Wei-Chieh Mu  1 , Rika Ohkubo  1 , Andrew Widjaja  1 , Danica Chen  2
Affiliations
Review

The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation

Wei-Chieh Mu et al. Mech Ageing Dev. 2020 Jun.

Abstract

Stem cell aging contributes to aging-associated tissue degeneration and dysfunction. Recent studies reveal a mitochondrial metabolic checkpoint that regulates stem cell quiescence and maintenance, and dysregulation of the checkpoint leads to functional deterioration of aged stem cells. Here, we present the evidence supporting the mitochondrial metabolic checkpoint regulating stem cell aging and demonstrating the feasibility to target this checkpoint to reverse stem cell aging. We discuss the mechanisms by which mitochondrial stress leads to stem cell deterioration. We speculate the therapeutic potential of targeting the mitochondrial metabolic checkpoint for rejuvenating aged stem cells and improving aging tissue functions.

Keywords: NLRP3; SIRT2; SIRT3; SIRT7; Stem cell aging.

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Figures

Figure 1.
Figure 1.. The mitochondrial metabolic checkpoint regulates stem cell quiescence, maintenance, and aging.
Upon stem cell transition from quiescence to proliferation, mitochondrial biogenesis takes place, which is associated with increased mitochondrial oxidative stress and mitochondrial protein folding stress. SIRT3 and SIRT7 govern mitochondrial stress in stem cells. Damaged mitochondria can also be cleared by mitochondrial fusion and fission, and mitophagy. Accumulation of mitochondrial stress results in stem cell death due to DNA mutations and activation of the NLRP3 inflammasome, which is regulated by SIRT2. During aging, the expression of SIRT2, SIRT3, and SIRT7 reduces in stem cells, resulting in the dysregulation of the mitochondrial metabolic checkpoint and loss of stem cell maintenance.
See this image and copyright information in PMC

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