LYRM7

LYR motif containing 7, also known as Complex III assembly factor LYRM7 or LYR motif-containing protein 7 is a protein that in humans is encoded by the LYRM7 gene.[1] The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene.[1]

Structure

The LYRM7 gene is located on the q arm of chromosome 5 at position 23.3 to 31.1, spans 34,512 base pairs, and has 5 exons.[1] The LYRM7 gene produces a 6.2 kDa protein composed of 53 amino acids, which is a soluble matrix protein with an N-terminal LYR motif.[2][3][4] LYRM7 is an assembly factor of the enzyme Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex) of the mitochondrial respiratory chain.[1][5]

Function

The LYRM7 gene encodes for an assembly factor necessary for the incorporation of the iron-sulfur cluster in the Rieske (Fe-S) protein (UQCRFS1),[5] which is an essential subunit of the Ubiquinol Cytochrome c Reductase (complex III) of the mitochondrial respiratory chain. LYRM7 acts by binding to the co-chaperone HSC20 of the Fe-S biogenesis machinery, which brings a cluster assembled on the main scaffold protein ISCU.[5] Direct binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates transfer of the Fe-S cluster from holo-ISCU to UQCRFS1.[5]

UQCRFS1, or Rieske (Fe-S) protein (UQCRFS1) is the last catalytic subunit added to the complex. Complex III is required for the catalysis of electron transfer from coenzyme Q to cytochrome c as well as the pumping of protons into the inner membrane from the matrix for the generation of an ATP-coupled electrochemical potential.[6][7]

Clinical significance

Variants of LYRM7 have been associated with mitochondrial complex III deficiency, nuclear 8 (MC3DN8). Mitochondrial complex III deficiency, nuclear 8 is a form of mitochondrial complex III deficiency, a disorder of Complex III of the mitochondrial respiratory chain. The deficiency is known to be highly variable in phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.[6][7] Pathogenic Mutations of the LYRM7 gene have included (c.73G>A), (c.214C>T), (c.37delA), and others.[8][9]

References
  1. "Entrez Gene: LYR motif containing 7". Retrieved 2018-08-01.Public Domain This article incorporates text from this source, which is in the public domain.
  2. Sánchez, E; Lobo, T; Fox, JL; Zeviani, M; Winge, DR; Fernández-Vizarra, E (March 2013). "LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial Complex III assembly in human cells". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1827 (3): 285–93. doi:10.1016/j.bbabio.2012.11.003. PMC 3570683. PMID 23168492.
  3. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  4. "Complex III assembly factor LYRM7". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  5. Maio, Nunziata; Kim, Ki Soon; Singh, Anamika; Rouault, Tracey A. (April 2017). "A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I–III". Cell Metabolism. 25 (4): 945–953.e6. doi:10.1016/j.cmet.2017.03.010. ISSN 1550-4131. PMID 28380382.
  6. "LYRM7 - Complex III assembly factor LYRM7 - Homo sapiens (Human) - LYRM7 gene & protein". www.uniprot.org. Retrieved 2018-07-31. This article incorporates [www.uniprot.org text] by UniProt available under the CC BY 4.0 license.
  7. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  8. Invernizzi F, Tigano M, Dallabona C, Donnini C, Ferrero I, Cremonte M, Ghezzi D, Lamperti C, Zeviani M (December 2013). "A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity". Hum. Mutat. 34 (12): 1619–22. doi:10.1002/humu.22441. PMC 4028993. PMID 24014394.
  9. Dallabona C, Abbink TE, Carrozzo R, Torraco A, Legati A, van Berkel CG, Niceta M, Langella T, Verrigni D, Rizza T, Diodato D, Piemonte F, Lamantea E, Fang M, Zhang J, Martinelli D, Bevivino E, Dionisi-Vici C, Vanderver A, Philip SG, Kurian MA, Verma IC, Bijarnia-Mahay S, Jacinto S, Furtado F, Accorsi P, Ardissone A, Moroni I, Ferrero I, Tartaglia M, Goffrini P, Ghezzi D, van der Knaap MS, Bertini E (March 2016). "LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance" (PDF). Brain. 139 (Pt 3): 782–94. doi:10.1093/brain/awv392. PMID 26912632.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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