Emerging roles of mitochondrial serine protease HtrA2 in neurodegeneration

Abstract

High temperature requirement mitochondrial serine protease A2 (HtrA2), commonly known as Omi/PRSS25, is primarily known for its protein quality control function. Loss of this prime function of the protein results in neurodegenerative diseases such as Parkinson's, Alzheimer's, Huntington's and certain forms of epilepsy. HtrA2 belongs to the family of evolutionary conserved proteases and is one of the core determinants of mitochondrial quality control. HtrA2 helps maintain normal mitochondrial functions during organelle biogenesis, metabolic remodelling and stress. It has been very well established that under stressful condition, HtrA2 is released from the mitochondria into the cytosol and facilitates apoptosis by binding to several members of the inhibitors of apoptosis protein (IAP) family. On the contrary, in vivo knockout studies showed a phenotype similar to Parkinson's suggesting its involvement in neurodegeneration along with maintenance of mitochondrial homeostasis. Therefore, presence of different cellular pathways and its unique multitasking ability makes HtrA2 a potential therapeutic target. This chapter discusses different facets of HtrA2 with main focus on its role as a quality control protease and its association with neurodegenerative disorders.