Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.

Journal Article (Journal Article)

Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility.

Full Text

Duke Authors

Cited Authors

  • Muoio, DM

Published Date

  • December 4, 2014

Published In

Volume / Issue

  • 159 / 6

Start / End Page

  • 1253 - 1262

PubMed ID

  • 25480291

Pubmed Central ID

  • PMC4765362

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.11.034


  • eng

Conference Location

  • United States