The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis

Figure 7

Mitochondrial dysfunction in the pathology of Huntington’s disease (HD). A CAG trinucleotide repeat expansion in the huntingtin (HTT) gene causes an array of mitochondrial dysfunctions in HD. Mutations in HTT are associated with a decrease in ATP synthesis and complex II and II activities. Mutant HTT also promotes mitochondrial apoptosis via its interaction with p53, leading to its enhanced expression and transcriptional activity that activates proapoptotic BAX. Damage and loss of mtDNA is another feature of HD that is attributed to the inhibition of PGC1α transcription by mutant HTT. Moreover, mutations in HTT contribute to mitochondrial fragmentation through the upregulation of mitochondrial fission proteins such as DRP1 and FIS1 and the downregulation of the fusion proteins, MFN1/2. Lastly, mutant HTT proteins can disrupt autophagy or mitophagy through its interaction with the autophagic adaptor, p62, and the mitophagic protein, BNIP3, respectively.