The TDH–GCN5L1–Fbxo15–KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells Academic Article Article uri icon

Overview

MeSH Major

  • Calcitriol
  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Transcription, Genetic

abstract

  • © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Self-renewing naive mouse embryonic stem cells (mESCs) contain few mitochondria, which increase in number and volume at the onset of differentiation. KBP (encoded by Kif1bp) is an interactor of the mitochondrial-associated kinesin Kif1Bα. We found that TDH, responsible for mitochondrial production of acetyl-CoA in mESCs, and the acetyltransferase GCN5L1 cooperate to acetylate Lys501 in KBP, allowing its recognition by and degradation via Fbxo15, an F-box protein transcriptionally controlled by the pluripotency core factors and repressed following differentiation. Defects in KBP degradation in mESCs result in an unscheduled increase in mitochondrial biogenesis, enhanced respiration and ROS production, and inhibition of cell proliferation. Silencing of Kif1Bα reverts the aberrant increase in mitochondria induced by KBP stabilization. Notably, following differentiation, Kif1bp−/− mESCs display impaired expansion of the mitochondrial mass and form smaller embryoid bodies. Thus, KBP proteolysis limits the accumulation of mitochondria in mESCs to preserve their optimal fitness, whereas KBP accumulation promotes mitochondrial biogenesis in differentiating cells.

publication date

  • March 20, 2017

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1038/ncb3491

PubMed ID

  • 28319092

Additional Document Info

start page

  • 341

end page

  • 351

volume

  • 19

number

  • 4