Mitochondrial Serine Protease HtrA2/Omi as a Potential Therapeutic Target

Md.   Shenuarin   Bhuiyan; Kohji      Fukunaga

Abstract

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 HrtA2 from its molecular origins, discusses its modulation and potential as a novel drug target, and considers future therapeutic perspectives.

Keywords: HtrA2, apoptosis, mitochondria, inhibitor of apoptosis proteins, caspases

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