Mitochondrial serine protease HtrA2/Omi as a potential therapeutic target.
Deregulation of apoptosis has been shown to contribute to the development of many diseases, including ischemia/reperfusion injury of organs, different types of cancer formation, as well as neurodegenerative and autoimmune disorders. Recently, the mitochondrial serine protease High temperature requirement A2 (HtrA2)/Omi has drawn attention as it played pivotal role in different pathological conditions. We critically discussed the rationale for therapeutically targeting HtrA2 signaling in pathological conditions and explore the molecular mechanisms of HtrA2 inhibition as a novel therapeutic strategy. The precise mode of action and importance of HtrA2 in mitochondrial quality control as well as in apoptosis in mammalian cells has been recently studied through biochemical, structural and genetic studies. This review introduces HtrA2 [correction of HrtA2] from its molecular origins, discusses its modulation and potential as a novel drug target, and considers future therapeutic perspectives.
Department of Pharmacology, Tohoku University, Japan.
Md Shenuarin
MS
Bhuiyan
Kohji
K
Fukunaga
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D011480:Protease Inhibitors / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D024101:Mitochondrial Proteins; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2