OMA1

Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1 gene.[5][6] 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.[7]

OMA1
Identifiers
Aliases	OMA1, 2010001O09Rik, DAB1, MPRP-1, YKR087C, ZMPpeptidase, OMA1 zinc metallopeptidase, MPRP1
External IDs	OMIM: 617081 MGI: 1914263 HomoloGene: 12070 GeneCards: OMA1
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p32.2-p32.1 Start 58,415,384 bp[1] End 58,546,802 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 C6 Start 103,313,812 bp[2] End 103,371,868 bp[2]
Gene ontology Molecular function • peptidase activity • hydrolase activity • metallopeptidase activity • metal ion binding • metalloendopeptidase activity Cellular component • membrane • integral component of membrane • mitochondrial membranes • mitochondrion • mitochondrial inner membrane Biological process • mitochondrial protein processing • energy homeostasis • response to stress • mitochondrion organization • cristae formation • protein quality control for misfolded or incompletely synthesized proteins • negative regulation of mitochondrial fusion • proteolysis • lipid metabolism • glucose metabolic process • diet induced thermogenesis • regulation of apoptotic process • positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	115209	67013
Ensembl	ENSG00000162600	ENSMUSG00000035069
UniProt	Q96E52	Q9D8H7
RefSeq (mRNA)	NM_145243	NM_025909
RefSeq (protein)	NP_660286	NP_080185
Location (UCSC)	Chr 1: 58.42 – 58.55 Mb	Chr 4: 103.31 – 103.37 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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).[8] The mature protein has a theoretical pI of 8.44.[9]

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.[6] 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.[10][11][12]

Clinical significance

OMA1 seems to play role in neurodegeneration[13] Several mutations in OMA1 were identified in Amyotrophic Lateral Sclerosis patients.

References

1. GRCh38: Ensembl release 89: ENSG00000162600 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035069 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: OMA1 zinc metallopeptidase".
6. 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.
7. 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.
8. "Uniprot: Q96E52 - OMA1_HUMAN".
9. Kozlowski LP (October 2016). "IPC - Isoelectric Point Calculator". Biology Direct. 11 (1): 55. doi:10.1186/s13062-016-0159-9. PMC 5075173. PMID 27769290. Archived from the original on 2013-04-29. Retrieved 2020-04-22.
10. 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.
11. 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.
12. 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.
13. 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.