Metabolic inflexibility is defined as an impaired capacity to switch between different energy substrates and is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Hence, understanding the mechanisms underlying proper metabolic flexibility is key to prevent the development of metabolic disease and physiological deterioration. An important downstream player in the effects of metabolic flexibility is the mitochondrion. The objective of this review was to describe how mitochondrial metabolism adapts to limited nutrient situations or caloric excess by changes in mitochondrial function or biogenesis, as well as to define the mechanisms propelling these changes. Altogether, this should pinpoint key regulatory points by which metabolic flexibility might be ameliorated in situations of metabolic disease.
EMBO Mol Med (2014) 6: 580–589
- Received December 14, 2013.
- Revision received January 31, 2014.
- Accepted February 4, 2014.
- © 2014 The Authors. Published under the terms of the CC BY 4.0 license
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