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===Protein=== | ===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).<ref>{{cite web|title=Uniprot: Q96E52 - OMA1_HUMAN|url= | 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).<ref>{{cite web|title=Uniprot: Q96E52 - OMA1_HUMAN|url=https://www.uniprot.org/uniprot/Q96E52}}</ref> The mature protein has a theoretical [[isoelectric point|pI]] of 8.44.<ref name="Kozlowski">{{cite journal | vauthors = Kozlowski LP | title = IPC - Isoelectric Point Calculator | journal = Biology Direct | volume = 11 | issue = 1 | pages = 55 | date = October 2016 | pmid = 27769290 | doi = 10.1186/s13062-016-0159-9 | url = http://isoelectric.ovh.org | pmc=5075173}}</ref> | ||
== Function == | == 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.<ref name="ReferenceA"/> 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.<ref>{{cite journal | vauthors = Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM | title = Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells | journal = The Journal of Cell Biology | volume = 187 | issue = 7 | pages = 959–66 | date = December 2009 | pmid = 20038677 | doi = 10.1083/jcb.200906083 | pmc=2806274}}</ref><ref>{{cite journal | vauthors = Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, Martinou JC, Westermann B, Rugarli EI, Langer T | title = Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1 | journal = The Journal of Cell Biology | volume = 187 | issue = 7 | pages = 1023–36 | date = December 2009 | pmid = 20038678 | doi = 10.1083/jcb.200906084 | pmc=2806285}}</ref><ref>{{cite journal | vauthors = McBride H, Soubannier V | title = Mitochondrial function: OMA1 and OPA1, the grandmasters of mitochondrial health | journal = Current Biology | volume = 20 | issue = 6 | pages = R274-6 | date = March 2010 | pmid = 20334834 | doi = 10.1016/j.cub.2010.02.011 }}</ref> | 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.<ref name="ReferenceA"/> 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.<ref>{{cite journal | vauthors = Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM | title = Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells | journal = The Journal of Cell Biology | volume = 187 | issue = 7 | pages = 959–66 | date = December 2009 | pmid = 20038677 | doi = 10.1083/jcb.200906083 | pmc=2806274}}</ref><ref>{{cite journal | vauthors = Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, Martinou JC, Westermann B, Rugarli EI, Langer T | title = Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1 | journal = The Journal of Cell Biology | volume = 187 | issue = 7 | pages = 1023–36 | date = December 2009 | pmid = 20038678 | doi = 10.1083/jcb.200906084 | pmc=2806285| url = https://archive-ouverte.unige.ch/unige:18363/ATTACHMENT01 }}</ref><ref>{{cite journal | vauthors = McBride H, Soubannier V | title = Mitochondrial function: OMA1 and OPA1, the grandmasters of mitochondrial health | journal = Current Biology | volume = 20 | issue = 6 | pages = R274-6 | date = March 2010 | pmid = 20334834 | doi = 10.1016/j.cub.2010.02.011 }}</ref> | ||
==Clinical significance== | ==Clinical significance== | ||
Latest revision as of 13:11, 4 November 2018
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| Location (UCSC) | n/a | n/a | |||||
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Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1 gene.[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]
Structure
Gene
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.
References
- ↑ "Entrez Gene: OMA1 zinc metallopeptidase".
- ↑ 2.0 2.1 Kaser 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. PMID 12963738.
- ↑ Jiang X, Jiang H, Shen Z, Wang X (October 2014). "Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 111 (41): 14782–7. doi:10.1073/pnas.1417253111. PMC 4205663. PMID 25275009.
- ↑ "Uniprot: Q96E52 - OMA1_HUMAN".
- ↑ Kozlowski LP (October 2016). "IPC - Isoelectric Point Calculator". Biology Direct. 11 (1): 55. doi:10.1186/s13062-016-0159-9. PMC 5075173. PMID 27769290.
- ↑ Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM (December 2009). "Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells". The Journal of Cell Biology. 187 (7): 959–66. doi:10.1083/jcb.200906083. PMC 2806274. PMID 20038677.
- ↑ Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, Martinou JC, Westermann B, Rugarli EI, Langer T (December 2009). "Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1". The Journal of Cell Biology. 187 (7): 1023–36. doi:10.1083/jcb.200906084. PMC 2806285. PMID 20038678.
- ↑ 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. PMID 20334834.
- ↑ Korwitz A, Merkwirth C, Richter-Dennerlein R, Tröder SE, Sprenger HG, Quirós PM, López-Otín C, Rugarli EI, Langer T (January 2016). "Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria". The Journal of Cell Biology. 212 (2): 157–66. doi:10.1083/jcb.201507022. PMC 4738383. PMID 26783299.