ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular adaptation to fuel use Academic Article uri icon

Overview

MeSH Major

  • Electron Transport Complex II
  • Hydrogen Peroxide
  • Mitochondria
  • Proto-Oncogene Proteins
  • Succinate Dehydrogenase
  • src-Family Kinases

abstract

  • Electron flux in the mitochondrial electron transport chain is determined by the superassembly of mitochondrial respiratory complexes. Different superassemblies are dedicated to receive electrons derived from NADH or FADH2, allowing cells to adapt to the particular NADH/FADH2 ratio generated from available fuel sources. When several fuels are available, cells adapt to the fuel best suited to their type or functional status (e.g., quiescent versus proliferative). We show that an appropriate proportion of superassemblies can be achieved by increasing CII activity through phosphorylation of the complex II catalytic subunit FpSDH. This phosphorylation is mediated by the tyrosine-kinase Fgr, which is activated by hydrogen peroxide. Ablation of Fgr or mutation of the FpSDH target tyrosine abolishes the capacity of mitochondria to adjust metabolism upon nutrient restriction, hypoxia/reoxygenation, and T cell activation, demonstrating the physiological relevance of this adaptive response.

publication date

  • June 3, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4274740

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2014.04.015

PubMed ID

  • 24856931

Additional Document Info

start page

  • 1020

end page

  • 33

volume

  • 19

number

  • 6