Abstract: Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4. Compelling evidence implicates impaired mitochondrial energetics, altered mitochondrial biogenesis and quality control, disturbed mitochondrial trafficking, oxidative stress and mitochondrial calcium dyshomeostasis in the pathogenesis of the disorder. Unfortunately, conventional mitochondrial-targeted molecules, such as cysteamine, creatine, coenzyme Q10, or triheptanoin, yielded negative or inconclusive results. However, future therapeutic strategies, aiming to restore mitochondrial biogenesis, improving the fission/fusion balance, and improving mitochondrial trafficking, could prove useful tools in improving the phenotype of Huntington’s disease and, used in combination with genome-editing methods, could lead to a cure for the disease.

Key words: antioxidants, calcium homeostasis, Huntington’s disease, mitochondrial biogenesis, mitochondrial fission/fusion, mitochondrial trafficking, oxidative phosphorylation, oxidative stress, SS peptides, therapeutic intervention