TABLE 1.

Known OXPHOS complex deficiencies in major neurodegenerative disorders

OXPHOS Complex	Huntington's Disease	Alzheimer's Disease	Parkinson's Disease	Amyotrophic Lateral Sclerosis
Complex I (NADH dehydrogenase or NADH:ubiquinone oxidoreductase)	Unaltered in brain of patients with HD, but reduced in skeletal muscle	Reduced in mitochondria, platelets, and lymphocytes from patients with AD and postmortem brain tissue	Impaired complex I activity is seen in substantia nigra, platelets; and skeletal muscle of patients with; complex I inhibitors are used to model PD	Increased in patients with familial ALS with SOD1 mutations, reduced in skeletal muscle samples from patients with sporadic ALS
Complex II (succinate dehydrogenase)	Reduced enzyme activity in brain of patients with advanced-stage HD and in muscle of transgenic mice; complex II inhibitors produce a HD phenotype in mice and primates	Reduced in mitochondria from patients with AD		Complex II + III activities are reduced in spinal cords of patients with ALS
Complex III (CoQ-cytochrome c reductase)	Reduced enzyme activity in patients with advanced-stage HD	Core 1 protein is significantly reduced in temporal cortex of patients with AD; also reduced in mitochondria, platelets, and lymphocytes from patients with AD and postmortem brain tissue		Complex I + III activities reduced in spinal cords of patients with ALS
Complex IV (cytochrome c oxidase)	Reduced COX activity in myoblasts and brain samples from patients with HD	Decreased activity and mRNA levels in brains, platelets and lymphocytes from AD patients	Reduced complex IV activity was reported in platelet mitochondria and skeletal muscle from patients with PD	Decreased COX activity in individual motor neurons, spinal cords and skeletal, muscle of patients with sporadic ALS; decreased COX subunits in G93A ALS mice
Complex V (ATP synthase)	ATP production is impaired in striatal cells from mutant htt mice	Reduced in mitochondria from patients with AD	Reduced enzyme activity for complex V in skin fibroblast cultures from patients with PD	Levels of different subunits (D, α, and β) are decreased in G93A ALS mice