Serine protease HTRA2, mitochondrial (HTRA2) (HTRA2)

Serine protease HTRA2, also known as Omi, is a nuclear-encoded mitochondrial protein that resides in the intermembrane space [UniProt, PubMed]. It functions as a critical regulator of mitochondrial quality control by acting as a chaperone and protease to degrade misfolded proteins [PubMed, Wikipedia]. Under conditions of cellular stress or apoptotic signaling, HTRA2 is released into the cytosol where it promotes programmed cell death through both caspase-dependent and caspase-independent pathways [UniProt, PubMed]. In the cytosol, it binds to and antagonizes Inhibitor of Apoptosis Proteins (IAPs) via its N-terminal IAP-binding motif, thereby facilitating caspase activation [UniProt, PubMed]. Mutations in the HTRA2 gene are associated with Parkinson's disease (PARK13), highlighting its essential role in neuronal survival and mitochondrial homeostasis [PubMed, GeneCards]. Conversely, its pro-apoptotic activity makes it a target of interest in cancer therapy and a mediator of damage in ischemic injuries [PubMed, MDPI]. Pharmacological modulation of HTRA2, such as with the inhibitor UCF-101, is being explored to mitigate tissue damage in neurodegeneration and ischemia [PubMed].

Other names

OmiHtrA2Serine protease 25PRSS25PARK13High temperature requirement protein A2

Inhibition of serine protease activity and antagonism of Inhibitor of Apoptosis Proteins (IAPs)