Autophagy and Stem Cells: Self-Eating for Self-Renewal

Abstract

Autophagy is a fundamental cell survival mechanism that allows cells to adapt to metabolic stress through the degradation and recycling of intracellular components to generate macromolecular precursors and produce energy. The autophagy pathway is critical for development, maintaining cellular and tissue homeostasis, as well as immunity and prevention of human disease. Defects in autophagy have been attributed to cancer, neurodegeneration, muscle and heart disease, infectious disease, as well as aging. While autophagy has classically been viewed as a passive quality control and general house-keeping mechanism, emerging evidence demonstrates that autophagy is an active process that regulates the metabolic status of the cell. Adult stem cells, which are long-lived cells that possess the unique ability to self-renew and differentiate into specialized cells throughout the body, have distinct metabolic requirements. Research in a variety of stem cell types have established that autophagy plays critical roles in stem cell quiescence, activation, differentiation, and self-renewal. Here, we will review the evidence demonstrating that autophagy is a key regulator of stem cell function and how defective stem cell autophagy contributes to degenerative disease, aging and the generation of cancer stem cells. Moreover, we will discuss the merits of targeting autophagy as a regenerative medicine strategy to promote stem cell function and improve stem cell-based therapies.

Keywords: aging; autophagy; cancer stem cell; mitochondria; quiescence; reprogramming; self-renewal; stem cells.