Cover StoryIn response to physiological and environmental stress, mitochondria require functional adaptation to match increased ATP demand and to maintain metabolic homeostasis. As cells are always exposed to fluctuations in energy supply and demand, intrinsic flexibility and allosteric control is partially supported by adjustments of protein concentrations.
However, in particular chronic impairments of energy balance, such as oversupply (during overnutrition) or the lack of demand (e.g. the lack of exercise), the limits of intrinsic flexibility and allosteric regulation, and possibly even the limits of proteomic adaptation, may be reached, thus establishing pathologies of the metabolic syndrome.
Walheim et al. combine quantitative mitochondrial respirometry (Seahorse technology) and proteomics (LC-MS/MS-based total protein approach) to understand how molecular changes translate to changes in mitochondrial energy transduction during diet-induced obesity (DIO) in the liver. The integrative analysis highlights the mitochondrial pyruvate carrier as prime element controlling respiration in the liver.
Furthermore, they show that mitochondrial lipid oxidation of DIO mice is specifically enhanced by an array of (partially novel) disease-related proteins controlling catabolism of fatty acids and amino acids. This proof-of-principle study shows that “respiromic” analyses are capable of revealing functional sets of stress-induced and disease-related proteins that can be further investigated as biomarkers or therapeutic targets.