Figure 4.

Regulation of pluripotency by autophagy. PSCs exhibit a high autophagic flux that is regulated by FOXO1, which coordinates the autophagy machinery gene program at the transcriptional level. High autophagic flux maintains appropriate levels of cellular pluripotency factors like OCT4, SOX2 and NANOG, and organelles like mitochondria (M). Inhibition of autophagy leads to accumulation of abnormal mitochondria and breakdown of pluripotency in spite of increased levels of pluripotency proteins. Activation of autophagy by AMPK is essential for both pluripotency maintenance and acquisition. Inactivation of mTOR by the pluripotency factors SOX2, KLK4 or c-MYC facilitates somatic cell reprogramming to pluripotency