IMMT explained
IMMT should not be confused with Institute of Minerals and Materials Technology.
Mitochondrial inner membrane protein is a protein that in humans is encoded by the IMMT gene.[1] [2] [3])
IMMT encodes an inner mitochondrial membrane (IMM) protein in the nucleus. It is posttranslational transported to the IMM. Mic60/Mitofilin (encoded by the IMMT gene) is a core subunit of the MICOS-complex, directly located next to cristae junctions (CJ). Human Mic60 exists in two isoforms of different size, anchored to the IMM via its N-terminus, while most of the protein is located to the inner mitochondrial space (IMS).
Function
Mic60 is evolutionary one of the oldest MICOS subunits as homologous were found in anaerobic prokaryotes. It is mainly present in two isoforms (ca. 88 and 90 kDa). In the brain, four isoforms are known, which differ in their isoelectric point due to different post-translational modifications. The amino terminus of Mic60 is anchored in the IM, while most of the protein is extended to the IMS. C-terminal Mic60 has a conserved mitofilin domain which is crucial for building the MICOS-complex. A central coiled-coil domain is required to enable protein-protein interactions.
Interactions
Mic60 indirectly interacts with all known MICOS-complex and SAM complex components. It directly interacts with Mic25, Mic19 and SAM50. Together with Mic25 and Mic19, Mic60 forms the Mic60-Mic19-Mic25 subcomplex. This subcomplex, especially Mic60, is crucial for the physical contact between the IMM and the outer mitochondrial membrane (OMM) via its interaction with SAM50. Mic60 also interacts with the translocase of the OMM (TOM) and the translocase of the IMM (TIM) to ensure the localization of Mic60 near to CJs. Through its interaction with TOM and TIM, Mic60 additionally influences the import of precursor proteins.
Localisation/Import
Mic60 is translated in the cytosol and translocated into the IMS via TOMM40. TIMM23 transports Mic60 into the IM, where a mitochondrial processing peptidase (MPP) cleaves of the N-terminal mitochondrial targeting signal (MTS). Mic60 is anchored in the IMM through its transmembrane (TM) domain.
Interactions
IMMT has been shown to interact with BAT2.[4])
Further reading
- Dawson SJ, White LA . Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin . The Journal of Infection . 24 . 3 . 317–320 . May 1992 . 1602151 . 10.1016/S0163-4453(05)80037-4 .
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- Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
- Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M . 6 . Generation and analysis of 280,000 human expressed sequence tags . Genome Research . 6 . 9 . 807–828 . September 1996 . 8889549 . 10.1101/gr.6.9.807 . free .
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
- Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, Wang XW, Conaway JW, Harris CC, Conaway RC, Reinberg D, Levens D . 6 . Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum . Cell . 104 . 3 . 353–363 . February 2001 . 11239393 . 10.1016/S0092-8674(01)00223-9 . 16066683 . free .
- Bernert G, Fountoulakis M, Lubec G . Manifold decreased protein levels of matrin 3, reduced motor protein HMP and hlark in fetal Down's syndrome brain . Proteomics . 2 . 12 . 1752–1757 . December 2002 . 12469345 . 10.1002/1615-9861(200212)2:12<1752::AID-PROT1752>3.0.CO;2-Y . 32160196 .
- Millar JK, Christie S, Porteous DJ . Yeast two-hybrid screens implicate DISC1 in brain development and function . Biochemical and Biophysical Research Communications . 311 . 4 . 1019–1025 . November 2003 . 14623284 . 10.1016/j.bbrc.2003.10.101 .
- Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–167 . January 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
- Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst CA, Landwehrmeyer BG, Lehrach H, Wanker EE . 6 . A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease . Molecular Cell . 15 . 6 . 853–865 . September 2004 . 15383276 . 10.1016/j.molcel.2004.09.016 . free .
- John GB, Shang Y, Li L, Renken C, Mannella CA, Selker JM, Rangell L, Bennett MJ, Zha J . 6 . The mitochondrial inner membrane protein mitofilin controls cristae morphology . Molecular Biology of the Cell . 16 . 3 . 1543–1554 . March 2005 . 15647377 . 551514 . 10.1091/mbc.E04-08-0697 .
- Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . 6 . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–968 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . free . 8235923 . 11858/00-001M-0000-0010-8592-0 .
- Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . 6 . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–814 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
- Camargo LM, Collura V, Rain JC, Mizuguchi K, Hermjakob H, Kerrien S, Bonnert TP, Whiting PJ, Brandon NJ . 6 . Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia . Molecular Psychiatry . 12 . 1 . 74–86 . January 2007 . 17043677 . 10.1038/sj.mp.4001880 . free .
- Xie J, Marusich MF, Souda P, Whitelegge J, Capaldi RA . The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11 . FEBS Letters . 581 . 18 . 3545–3549 . July 2007 . 17624330 . 10.1016/j.febslet.2007.06.052 . 726629 . free .
Notes and References
- Gieffers C, Korioth F, Heimann P, Ungermann C, Frey J . Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms . Experimental Cell Research . 232 . 2 . 395–399 . May 1997 . 9168817 . 10.1006/excr.1997.3539 .
- Icho T, Ikeda T, Matsumoto Y, Hanaoka F, Kaji K, Tsuchida N . A novel human gene that is preferentially transcribed in heart muscle . Gene . 144 . 2 . 301–306 . July 1994 . 8039717 . 10.1016/0378-1119(94)90394-8 .
- Web site: Entrez Gene: IMMT inner membrane protein, mitochondrial (mitofilin).
- Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–167 . January 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .