Moreover, mHTT severely impairs ATP production and respiration rate, suggesting that dysregulated energy metabolism may be a key feature of HD.219 Mounting evidence indicates that impaired mitochondrial clearance in HD reflects dysregulation of mitophagic pathways.220,221 mHTT shows reduced binding affinity with the selective autophagy receptor p62220 and impaired ULK1/PI3KC3 complex formation, hindering autophagosome–lysosome fusion.221 Consequently, damaged mitochondria accumulate, amplifying ROS production and caspase activation. This evidence concerns the gene ULK1 and Huntington disease.