The Role of Autophagy and Mitophagy in Huntington’s Disease

Abstract

Huntington’s disease (HD) is an inherited autosomal-dominant neurodegenerative disorder that occurs due to mutations in the polyglutamine expansions of the Huntingtin protein (Htt). HD is characterised by the loss of cognitive and motor functions, as well as the development of emotional and psychiatric disturbances. The HD pathology is manifested through the cellular changes that arise due to the toxic functions of mutant Htt (mHtt). Autophagy is a lysosomal pathway that functions to remove damaged intracellular components while mitophagy is a selective form of autophagy involving mitochondria; and PINK1/Parkin-mediated mitophagy is the most well-understood pathway. Mitochondrial dysfunction and defects in mitophagy can be linked to the pathogenesis of HD. Previous research has shown that the presence of mHtt hinders mitophagy; while PINK1/Parkin-mediated mitophagy provides neuroprotection in HD. Hence, this review discusses the roles and regulations of mitophagy, along with an overview of mitophagy in HD.

Keywords

• huntington’s disease
• autophagy
• mitophagy