Dietary Macronutrient Management to Treat Mitochondrial Dysfunction in Parkinson's Disease

Abstract

Mitochondrial dysfunction has been demonstrated to play an important role in the pathogenesis of Parkinson's disease (PD). The products of several PD-associated genes, including alpha-synuclein, parkin, pink1, protein deglycase DJ-1, and leucine rich repeat kinase 2, have important roles in mitochondrial biology. Thus, modifying mitochondrial function could be a potential therapeutic strategy for PD. Dietary management can alter mitochondrial function as shifts in dietary macronutrients and their ratios in food can alter mitochondrial energy metabolism, morphology and dynamics. Our studies have established that a low protein to carbohydrate (P:C) ratio can increase lifespan, motor ability and mitochondrial function in a parkin mutant Drosophila model of PD. In this review, we describe mitochondrial dysfunction in PD patients and models, and dietary macronutrient management strategies to reverse it. We focus on the effects of protein, carbohydrate, fatty acids, and their dietary ratios. In addition, we propose potential mechanisms that can improve mitochondrial function and thus reverse or delay the onset of PD.

Keywords: diet; macronutrients; mitochondria; oxidative stress.

Figure 1

Potential mechanisms by which low protein and high carbohydrate diet can prevent mitochondrial dysfunction in Parkinson’s disease. Low P:C ratio diet can enable mitochondrial independent respiration causing low reactive oxygen species (ROS) generation which may lead to low oxidative stress. Low P:C ratio diet may also facilitate lower ROS generation preventing lipid peroxidation. Low P:C ratio diet can promote mitochondrial fusion and function. The bottom rectangle is the macronutrient (low P:C ratio diet). The ovals represent the potential mechanisms and processes of how macronutrients can affect mitochondrial functions. The top blue filled rectangles are the ways that can lead to healthy and efficient mitochondria in PD.

Figure 2

Potential mechanisms by which fatty acid can prevent mitochondrial dysfunction in PD. Fatty acid can be involved in mitochondrial function in three possible ways. First, fatty acid (stearic acid) can act as a signalling molecule to promote mitochondrial fusion. Second, saturated fatty acids can be directly incorporated into leaky mitochondrial membranes. Third, saturated fatty acids can be incorporated into lipid membranes making them resistant to peroxidation. The bottom rectangle is the macronutrient (saturated fatty acid). The ovals represent the potential mechanisms and processes of how the macronutrient can affect mitochondrial functions. The top blue filled rectangles are the ways that can lead to healthy and efficient mitochondria in PD.