Rhomboid proteases in mitochondria and plastids: Keeping organelles in shape

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1833, Issue 2, 2013, Pages 371-380

  Jeyaraju, Danny V ^a   Sood, Aditi ^a   Laforce Lavoie, Audrey ^a   Pellegrini, Luca ^a,b  

^a CENTRE DE RECHERCHE DE L INSTITUT UNIVERSITAIRE EN SANTÉ MENTALE DE QUÉBEC   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

Author keywords

Hax1; Mitophagy; Opa1; Parl; PINK1; Rhomboid protease

Indexed keywords

CYTOCHROME C PEROXIDASE; FUNGAL PROTEIN; HISTIDINE; PROTEIN PARL; PROTEINASE; RHOMBOID; RHOMBOID 1; RHOMBOID 2; RHOMBOID 7; SERINE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CELL ORGANELLE; CELL SHAPE; FUNGAL GENE; MITOCHONDRION; NONHUMAN; PARKINSON DISEASE; PHYLOGENY; PLASTID; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION;

ANIMALIA; EUKARYOTA; MAMMALIA;

EID: 84871806637     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2012.05.019     Document Type: Review

References (100)

1. López-Otín C., Bond J.S. Proteases: multifunctional enzymes in life and disease. J. Biol. Chem. 2008, 283:30433-30437.
2. Rawson R.B., Zelenski N.G., Nijhawan D., Ye J., Sakai J., Hasan M.T., Chang T.Y., Brown M.S., Goldstein J.L. Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol. Cell 1997, 1:47-57.
3. Wolfe M.S. Intramembrane-cleaving proteases. J. Biol. Chem. 2009, 284:13969-13973.
4. Urban S., Freeman M. Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol. Cell 2003, 11:1425-1434.
5. Strisovsky K., Sharpe H.J., Freeman M. Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates. Mol. Cell 2009, 36:1048-1059.
6. Wolfe M.S. Intramembrane proteolysis. Chem. Rev. 2009, 109:1599-1612.
7. Brown M.S., Ye J., Rawson R.B., Goldstein J.L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 2000, 100:391-398.
8. Weihofen A., Martoglio B. Intramembrane-cleaving proteases: controlled liberation of proteins and bioactive peptides. Trends Cell Biol. 2003, 13:71-78.
9. Brown M.S., Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997, 89:331-340.
10. De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J.S., Schroeter E.H., Schrijvers V., Wolfe M.S., Ray W.J., Goate A., Kopan R. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 1999, 398:518-522.
11. De Strooper B., Saftig P., Craessaerts K., Vanderstichele H., Guhde G., Annaert W., Von Figura K., Van Leuven F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 1998, 391:387-390.
12. Wolfe M.S. Structure, mechanism and inhibition of gamma-secretase and presenilin-like proteases. Biol. Chem. 2010, 391:839-847.
13. Weihofen A., Binns K., Lemberg M.K., Ashman K., Martoglio B. Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 2002, 296:2215-2218.
14. Lemberg M.K., Martoglio B. On the mechanism of SPP-catalysed intramembrane proteolysis; conformational control of peptide bond hydrolysis in the plane of the membrane. FEBS Lett. 2004, 564:213-218.
15. Urban S., Lee J.R., Freeman M. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 2001, 107:173-182.
16. Mayer U., Nüsslein-Volhard C. A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev. 1988, 2:1496-1511.
17. Koonin E.V., Makarova K.S., Rogozin I.B., Davidovic L., Letellier M.C., Pellegrini L. The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol. 2003, 4:R19.
18. Hill R.B., Pellegrini L. The PARL family of mitochondrial rhomboid proteases. Semin. Cell Dev. Biol. 2010, 21:582-592.
19. Lee J.R., Urban S., Garvey C.F., Freeman M. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell 2001, 107:161-171.
20. Urban S., Lee J.R., Freeman M. A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J. 2002, 21:4277-4286.
21. Wasserman J.D., Urban S., Freeman M. A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling. Genes Dev. 2000, 14:1651-1663.
22. Reyes-Prieto A., Weber A.P., Bhattacharya D. The origin and establishment of the plastid in algae and plants. Annu. Rev. Genet. 2007, 41:147-168.
23. Lemberg M.K., Freeman M. Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases. Genome Res. 2007, 17:1634-1646.
24. Zettl M., Adrain C., Strisovsky K., Lastun V., Freeman M. Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 2011, 145:79-91.
25. Adrain C., Zettl M., Christova Y., Taylor N., Freeman M. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 2012, 335:225-228.
26. McIlwain D.R., Lang P.A., Maretzky T., Hamada K., Ohishi K., Maney S.K., Berger T., Murthy A., Duncan G., Xu H.C., Lang K.S., Häussinger D., Wakeham A., Itie-Youten A., Khokha R., Ohashi P.S., Blobel C.P., Mak T.W. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science 2012, 335:229-232.
27. Greenblatt E.J., Olzmann J.A., Kopito R.R. Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum. Nat. Struct. Mol. Biol. 2011, 18:1147-1152.
28. Wang Y., Zhang Y., Ha Y. Crystal structure of a rhomboid family intramembrane protease. Nature 2006, 444:179-180.
29. Wu Z., Yan N., Feng L., Oberstein A., Yan H., Baker R.P., Gu L., Jeffrey P.D., Urban S., Shi Y. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat. Struct. Mol. Biol. 2006, 13:1084-1091.
30. Ben-Shem A., Fass D., Bibi E. Structural basis for intramembrane proteolysis by rhomboid serine proteases. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:462-466.
31. Lemieux M.J., Fischer S.J., Cherney M.M., Bateman K.S., James M.N. The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:750-754.
32. Wang Y., Ha Y. Open-cap conformation of intramembrane protease GlpG. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:2098-2102.
33. Wang Y., Maegawa S., Akiyama Y., Ha Y. The role of L1 loop in the mechanism of rhomboid intramembrane protease GlpG. J. Mol. Biol. 2007, 374:1104-1113.
34. Baker R.P., Young K., Feng L., Shi Y., Urban S. Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:8257-8262.
35. Urban S. Taking the plunge: integrating structural, enzymatic and computational insights into a unified model for membrane-immersed rhomboid proteolysis. Biochem. J. 2010, 425:501-512.
36. Ekici O.D., Paetzel M., Dalbey R.E. Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration. Protein Sci. 2008, 17:2023-2037.
37. Polgár L. The catalytic triad of serine peptidases. Cell. Mol. Life Sci. 2005, 62:2161-2172.
38. Jeyaraju D.V., McBride H.M., Hill R.B., Pellegrini L. Structural and mechanistic basis of Parl activity and regulation. Cell Death Differ. 2011, 18:1531-1539.
39. Pellegrini L., Scorrano L. A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis. Cell Death Differ. 2007, 14:1275-1284.
40. Cipolat S., Rudka T., Hartmann D., Costa V., Serneels L., Craessaerts K., Metzger K., Frezza C., Annaert W., D'Adamio L., Derks C., Dejaegere T., Pellegrini L., D'Hooge R., Scorrano L., De Strooper B. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 2006, 126:163-175.
41. Frezza C., Cipolat S., Martins de Brito O., Micaroni M., Beznoussenko G.V., Rudka T., Bartoli D., Polishuck R.S., Danial N.N., De Strooper B., Scorrano L. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 2006, 126:177-189.
42. Bondar A.N., del Val C., White S.H. Rhomboid protease dynamics and lipid interactions. Structure 2009, 17:395-405.
43. Urban S., Wolfe M.S. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:1883-1888.
44. Urban S. Rhomboid proteins: conserved membrane proteases with divergent biological functions. Genes Dev. 2006, 20:3054-3068.
45. Freeman M. Rhomboid proteases and their biological functions. Annu. Rev. Genet. 2008, 42:191-210.
46. Lichtenthaler S.F. Cell biology. Sheddase gets guidance. Science 2012, 335:179-180.
47. Stevenson L.G., Strisovsky K., Clemmer K.M., Bhatt S., Freeman M., Rather P.N. Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:1003-1008.
48. Gallio M., Sturgill G., Rather P., Kylsten P. A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:12208-12213.
49. Baker R.P., Wijetilaka R., Urban S. Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLoS Pathog. 2006, 2:e113.
50. Santos J.M., Ferguson D.J., Blackman M.J., Soldati-Favre D. Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode. Science 2011, 331:473-477.
51. Urban S. Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms. Nat. Rev. Microbiol. 2009, 7:411-423.
52. Karakasis K., Taylor D., Ko K. Uncovering a link between a plastid translocon component and rhomboid proteases using yeast mitochondria-based assays. Plant Cell Physiol. 2007, 48:655-661.
53. Herlan M., Vogel F., Bornhovd C., Neupert W., Reichert A.S. Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J. Biol. Chem. 2003, 278:27781-27788.
54. Herlan M., Bornhövd C., Hell K., Neupert W., Reichert A.S. Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor. J. Cell Biol. 2004, 165:167-173.
55. Esser K., Tursun B., Ingenhoven M., Michaelis G., Pratje E. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1. J. Mol. Biol. 2002, 323:835-843.
56. McQuibban G.A., Saurya S., Freeman M. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 2003, 423:537-541.
57. Guan K., Farh L., Marshall T.K., Deschenes R.J. Normal mitochondrial structure and genome maintenance in yeast requires the dynamin-like product of the MGM1 gene. Curr. Genet. 1993, 24:141-148.
58. Hermann G.J., Thatcher J.W., Mills J.P., Hales K.G., Fuller M.T., Nunnari J., Shaw J.M. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 1998, 143:359-373.
59. Rapaport D., Brunner M., Neupert W., Westermann B. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J. Biol. Chem. 1998, 273:20150-20155.
60. Sesaki H., Jensen R.E. UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell Biol. 2001, 152:1123-1134.
61. DeVay R.M., Dominguez-Ramirez L., Lackner L.L., Hoppins S., Stahlberg H., Nunnari J. Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. J. Cell Biol. 2009, 186:793-803.
62. Sesaki H., Southard S.M., Hobbs A.E., Jensen R.E. Cells lacking Pcp1p/Ugo2p, a rhomboid-like protease required for Mgm1p processing, lose mtDNA and mitochondrial structure in a Dnm1p-dependent manner, but remain competent for mitochondrial fusion. Biochem. Biophys. Res. Commun. 2003, 308:276-283.
63. McQuibban G.A., Saurya S., Freeman M. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 2003, 423:537-541.
64. McQuibban G.A., Lee J.R., Zheng L., Juusola M., Freeman M. Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. Curr. Biol. 2006, 16:982-989.
65. Rahman M., Kylsten P. Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning mitochondria. Biochem. Biophys. Res. Commun. 2011, 414(2):315-320.
66. Park J., Lee S.B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., Shong M., Kim J.M., Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 2006, 441:1157-1161.
67. Clark I.E., Dodson M.W., Jiang C., Cao J.H., Huh J.R., Seol J.H., Yoo S.J., Hay B.A., Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 2006, 441:1162-1166.
68. Whitworth A.J., Lee J.R., Ho V.M., Flick R., Chowdhury R., McQuibban G.A. Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin. Dis. Model. Mech. 2008, 1:168-174. (discussion 173).
69. Poole A.C., Thomas R.E., Andrews L.A., McBride H.M., Whitworth A.J., Pallanck L.J. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:1638-1643.
70. Wolozin B., Iwasaki K., Vito P., Ganjei J.K., Lacanà E., Sunderland T., Zhao B., Kusiak J.W., Wasco W., D'Adamio L. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 1996, 274:1710-1713.
71. Vito P., Ghayur T., D'Adamio L. Generation of anti-apoptotic presenilin-2 polypeptides by alternative transcription, proteolysis, and caspase-3 cleavage. J. Biol. Chem. 1997, 272:28315-28320.
72. Pellegrini L., Passer B.J., Canelles M., Lefterov I., Ganjei J.K., Fowlkes B.J., Koonin E.V., D'Adamio L. PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and-2. J. Alzheimers Dis. 2001, 3:181-190.
73. Jeyaraju D.V., Xu L., Letellier M.C., Bandaru S., Zunino R., Berg E.A., McBride H.M., Pellegrini L. Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:18562-18567.
74. Cipolat S., Martins de Brito O., Dal Zilio B., Scorrano L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:15927-15932.
75. Klein C., Grudzien M., Appaswamy G., Germeshausen M., Sandrock I., Schäffer A.A., Rathinam C., Boztug K., Schwinzer B., Rezaei N., Bohn G., Melin M., Carlsson G., Fadeel B., Dahl N., Palmblad J., Henter J.I., Zeidler C., Grimbacher B., Welte K. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat. Genet. 2007, 39:86-92.
76. Fadeel B., Grzybowska E. HAX-1: a multifunctional protein with emerging roles in human disease. Biochim. Biophys. Acta 2009, 1790(10):1139-1148.
77. Chao J.R., Parganas E., Boyd K., Hong C.Y., Opferman J.T., Ihle J.N. Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons. Nature 2008, 452:98-102.
78. Jeyaraju D.V., Cisbani G., De Brito O.M., Koonin E.V., Pellegrini L. Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis. Cell Death Differ. 2009, 16:1622-1629.
79. Vafiadaki E., Arvanitis D.A., Pagakis S.N., Papalouka V., Sanoudou D., Kontrogianni-Konstantopoulos A., Kranias E.G. The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival. Mol. Biol. Cell 2009, 20:306-318.
80. Simmen T. Hax-1: a regulator of calcium signaling and apoptosis progression with multiple roles in human disease. Expert Opin. Ther. Targets 2011, 15(6):741-751.
81. Cavnar P.J., Berthier E., Beebe D.J., Huttenlocher A. Hax1 regulates neutrophil adhesion and motility through RhoA. J. Cell Biol. 2011, 193:465-473.
82. Sík A., Passer B.J., Koonin E.V., Pellegrini L. Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide. J. Biol. Chem. 2004, 279:15323-15329.
83. Civitarese A.E., MacLean P.S., Carling S., Kerr-Bayles L., McMillan R.P., Pierce A., Becker T.C., Moro C., Finlayson J., Lefort N., Newgard C.B., Mandarino L., Cefalu W., Walder K., Collier G.R., Hulver M.W., Smith S.R., Ravussin E. Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL. Cell Metab. 2010, 11:412-426.
84. Jeyaraju D.V., Cisbani G., Pellegrini L. Calcium regulation of mitochondria motility and morphology. Biochim. Biophys. Acta 2009, 1787:1363-1373.
85. Chen H., Chan D.C. Physiological functions of mitochondrial fusion. Ann. N. Y. Acad. Sci. 2010, 1201:21-25.
86. Shi G., Lee J.R., Grimes D.A., Racacho L., Ye D., Yang H., Ross O.A., Farrer M., McQuibban G.A., Bulman D.E. Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease. Hum. Mol. Genet. 2011, 20:1966-1974.
87. Ehses S., Raschke I., Mancuso G., Bernacchia A., Geimer S., Tondera D., Martinou J.C., Westermann B., Rugarli E.I., Langer T. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J. Cell Biol. 2009, 187:1023-1036.
88. Head B., Griparic L., Amiri M., Gandre-Babbe S., van der Bliek A.M. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J. Cell Biol. 2009, 187:959-966.
89. Jin S.M., Lazarou M., Wang C., Kane L.A., Narendra D.P., Youle R.J. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 2010, 191:933-942.
90. Dauer W., Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003, 39:889-909.
91. Lesage S., Brice A. Parkinson's disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet. 2009, 18:R48-R59.
92. Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M., Harvey K., Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., Albanese A., Nussbaum R., González-Maldonado R., Deller T., Salvi S., Cortelli P., Gilks W.P., Latchman D.S., Harvey R.J., Dallapiccola B., Auburger G., Wood N.W. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004, 304:1158-1160.
93. Gegg M.E., Cooper J.M., Chau K.Y., Rojo M., Schapira A.H., Taanman J.W. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum. Mol. Genet. 2010, 19:4861-4870.
94. Chan N.C., Salazar A.M., Pham A.H., Sweredoski M.J., Kolawa N.J., Graham R.L., Hess S., Chan D.C. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum. Mol. Genet. 2011, 20:1726-1737.
95. Ziviani E., Tao R.N., Whitworth A.J. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:5018-5023.
96. Deas E., Plun-Favreau H., Gandhi S., Desmond H., Kjaer S., Loh S.H., Renton A.E., Harvey R.J., Whitworth A.J., Martins L.M., Abramov A.Y., Wood N.W. PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum. Mol. Genet. 2011, 20:867-879.
97. Meissner C., Lorenz H., Weihofen A., Selkoe D.J., Lemberg M.K. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J. Neurochem. 2011, 117:856-867.
98. Amarneh B., Rawson R.B. Rhomboid proteases: familiar features in unfamiliar phases. Mol. Cell 2009, 36:922-923.
99. Schäfer A., Zick M., Kief J., Steger M., Heide H., Duvezin-Caubet S., Neupert W., Reichert A.S. Intramembrane proteolysis of Mgm1 by the mitochondrial rhomboid protease is highly promiscuous regarding the sequence of the cleaved hydrophobic segment. J. Mol. Biol. 2010, 401:182-193.
100. MacKenzie K.R., Prestegard J.H., Engelman D.M. A transmembrane helix dimer: structure and implications. Science 1997, 276:131-133.