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Mitochondria are an important regulator of organismal fitness and the key energy converting organelle. The flow of energy in eukaryotes involves the conversion of macronutrients to form substrates that drive mitochondrial respiration. Changing the relative ratio of dietary macronutrients can influence metabolic flexibility and alter the production of mitochondrial metabolites, such as reactive oxygen species (ROS), which can influence mitochondrial functions and affect the organismal health. In this review, we describe the differences in mitochondrial output due to dietary macronutrient composition in individuals with Complex I mutations. Non-synonymous mutations in mitochondrial Complex I subunits are a common cause of early-onset mitochondrial diseases. We discuss the possibility of manipulating macronutrient ratios as a treatment for some cases of mild mitochondrial dysfunction.

Can we alter dietary macronutrient compositions and alleviate mitochondrial disease?