Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1gene.[1][2] As a metalloprotease, this protein is a substantial component of the quality control system in the inner membrane of mitochondria. Being activated by enzyme Bax and Bak, mitochondrial protease OMA1 promotes cytochrome c release which subsequently induces apoptosis.[3]
The gene OMA1 encodes a metalloprotease, a founding member of a conserved family of membrane-embedded metallopeptidases in mitochondria. The human gene has 9 exons and locates at chromosome band 1p32.2-p32.1
Protein
The human protein metalloendopetidase OMA1, mitochondrial is 60.1 kDa in size and composed of 524 amino acids with mitochondrial transition peptide (position 1-13).[4] The mature protein has a theoretical pI of 8.44.[5]
Function
The inner membrane of mitochondrial houses two AAA proteases and these membrane-embedded peptidases were termed m- and i-AAA proteases to indicate their different topology in the inner membrane. The m-AAA protease is facing the matrix and the i-AAA protease is facing the intermembrane space. OMA1 was shown to share an overlapping proteolytic activity with m-AAA protease. However, OMA1 doesn't completely regulate the turnover of a model substrate, Oxa1, as what the m-AAA protease does. On the contrary, Oma1 only generates N- and C-terminal proteolytic fragments.[2] It has been showed that the mammalian mitochondrial inner membrane fusion protein OPA1 can be degraded by OMA1 when mitochondria lose membrane potential or adenosine triphosphate. Such inducible proteolysis acts as a regulatory mechanism to proteolytically inactivate OPA1, thus preventing the fusion of the mitochondrial network.[6][7][8]
Clinical significance
OMA1 seems to play role in neurodegeneration[9] Several mutations in OMA1 were identified in Amyotrophic Lateral Sclerosis patients.
↑ 2.02.1Kaser M, Kambacheld M, Kisters-Woike B, Langer T (November 2003). "Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease". The Journal of Biological Chemistry. 278 (47): 46414–23. doi:10.1074/jbc.m305584200. PMID12963738.
↑McBride H, Soubannier V (March 2010). "Mitochondrial function: OMA1 and OPA1, the grandmasters of mitochondrial health". Current Biology. 20 (6): R274–6. doi:10.1016/j.cub.2010.02.011. PMID20334834.