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Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function. (Antioxid Redox Signal, July 2017)

Tan DQ1, Suda T2,3.

Author information
1 National University of Singapore, Cancer Science Institute of Singapore, Singapore, Singapore; A0074009@u.nus.edu.
2 National University of Singapore, Cancer Science Institute of Singapore, Singapore, Singapore.
3 Kumamoto University, International Research Center for Medical Science, Kumamoto, Japan; sudato@z3.keio.jp.

Abstract
SIGNIFICANCE: The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remains of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal and differentiation; all of which can be influenced by ROS levels. Recent advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments; particularly those of hematopoietic, neural and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest.

CRITICAL ISSUES: Here, we explore the reciprocal relationship between ROS and stem cells; with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells; especially oxidative damage of lipids, proteins and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics and distribution (i.e. segregation and transfer)) in stem cell redox homeostasis.

FUTURE DIRECTIONS: Therefore, elucidating the intricate links between mitochondria, cellular metabolism and redox homeostasis are envisioned to be critical for our understanding of ROS in stem cell biology; and its therapeutic relevance in regenerative medicine.

PMID: 28708000