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

Published

Journal Article

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 catabolism. Cell fate and metabolic state are linked by transcriptional regulators, such as IRF4 and FoxO1, with dual roles in lineage and metabolic choice. Instructing some cells to utilize nutrients for anabolism and differentiation while other cells catabolically self-digest and self-renew may enable growth and repair in metazoa.

Full Text

Duke Authors

Cited Authors

  • Adams, WC; Chen, Y-H; Kratchmarov, R; Yen, B; Nish, SA; Lin, W-HW; Rothman, NJ; Luchsinger, LL; Klein, U; Busslinger, M; Rathmell, JC; Snoeck, H-W; Reiner, SL

Published Date

  • December 20, 2016

Published In

Volume / Issue

  • 17 / 12

Start / End Page

  • 3142 - 3152

PubMed ID

  • 28009285

Pubmed Central ID

  • 28009285

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.11.065

Language

  • eng

Conference Location

  • United States