Mitophagy in Huntington's disease

Abstract

Huntington's disease (HD), as well as Parkinson's disease and Alzheimer's disease, belong to a group of neurodegenerative diseases characterized by common features, such as the progressive loss of neurons and the presence of pathogenic forms of misfolded protein aggregates. A quality control system such as autophagy is crucial for the clearance of protein aggregates and dysfunctional organelles and thus essential for the maintenance of neuronal homeostasis. The constant high energy demand of neuronal tissue links neurodegeneration to mitochondria. Inefficient removal of damaged mitochondria is thought to contribute to the pathogenesis of neurodegenerative diseases such as HD. In addition, direct involvement of the huntingtin protein in the autophagic machinery has been described. In this review, we focus on mitophagy, a selective form of autophagy responsible for mitochondrial turnover. We also discuss the relevance of pharmacological regulation of mitophagy in the future therapeutic approach to neurodegenerations, including HD.

Keywords: Huntington's disease; Mitochondria; Mitophagy; Mitophagy adaptors; Pharmacological induction of mitophagy.