Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal.

ABSTRACT: Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing metabolic states. Differentiation driven by an anabolic constellation of PI3K/mTOR activation, aerobic glycolysis, inhibited autophagy, mitochondrial stasis, and ROS production is balanced with self-renewal maintained by a catabolic constellation of AMPK activation, mitochondrial elimination, oxidative metabolism, and maintenance of FoxO1 activity. Perturbations up and down the metabolic pathways shift the balance of nutritive constellations and cell fate owing to self-reinforcement and reciprocal inhibition between anabolism and catabol

SUBMITTER: Adams WC 

PROVIDER: S-EPMC5189677 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature