Abstract
FtsH, a member of the AAA (ATPases associated with a variety of cellular activities) family of proteins, is an ATP-dependent protease of ∼71 kDa anchored to the inner membrane. It plays crucial roles in a variety of cellular processes. It is responsible for the degradation of both membrane and cytoplasmic substrate proteins. Substrate proteins are unfolded and translocated through the central pore of the ATPase domain into the proteolytic chamber, where the polypeptide chains are processively degraded into short peptides. FtsH is not only involved in the proteolytic elimination of unnecessary proteins, but also in the proteolytic regulation of a number of cellular functions. Its role in proteolytic regulation is achieved by one of two approaches, either the cellular levels of a regulatory protein are controlled by processive degradation of the entire protein, or the activity of a particular substrate protein is modified by processing. In the latter case, protein processing requires the presence of a stable domain within the substrate. Since FtsH does not have a robust unfolding activity, this stable domain is sufficient to abort processive degradation of the protein – resulting in release of a stable protein fragment.
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References
Bieniossek C, Niederhauser B, Baumann UM (2009) The crystal structure of apo-FtsH reveals domain movements necessary for substrate unfolding and translocation. Proc Natl Acad Sci U S A 106(51):21579–21584
Krzywda S, Brzozowski AM, Verma C, Karata K (2002) The crystal structure of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli at 1.5 A resolution. Structure 10(8):1073–1083
Langklotz S, Baumann U, Narberhaus F (2012) Structure and function of the bacterial AAA protease FtsH. Biochim Biophys Acta 1823(1):40–48
Ogura T, Okuno T, Suno R, Akiyama Y (2013) FtsH protease. In: Rawlings ND, Salvesen G (eds) Handbook of Proteolytic Enzymes, 3rd edn. Elsevier, pp 685–692
Okuno T, Ogura T (2008) FtsH protease, a eubacterial membrane-bound AAA protease. In: Kutejova E (ed) ATP-Dependent Proteases, Research Signport, pp 87–114
Suno R, Niwa H, Tsuchiya D, Zhang X et al (2006) Structure of the whole cytosolic region of ATP-dependent protease FtsH. Mol Cell 22(5):575–585
Asahara Y, Atsuta K, Motohashi K, Taguchi H et al (2000) FtsH recognizes proteins with unfolded structure and hydrolyzes the carboxyl side of hydrophobic residues. J Biochem 127(5):931–937
Gerdes F, Tatsuta T, Langer T (2012) Mitochondrial AAA proteases – towards a molecular understanding of membrane-bound proteolytic machines. Biochim Biophys Acta 1823(1):49–55
Nixon PJ, Michoux F, Yu J, Boehm M et al (2010) Recent advances in understanding the assembly and repair of photosystem II. Ann Bot 106(1):1–16
Rugarli EI, Langer T (2006) Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia. Trends Mol Med 12(6):262–269
Sakamoto W (2006) Protein degradation machineries in plastids. Annu Rev Plant Biol 57:599–621
Herman C, Thevenet D, D’Ari R, Bouloc P (1995) Degradation of sigma 32, the heat shock regulator in Escherichia coli, is governed by HflB. Proc Natl Acad Sci U S A 92(8):3516–3520
Tomoyasu T, Gamer J, Bukau B, Kanemori M et al (1995) Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32. EMBO J 14(11):2551–2560
Obrist M, Langklotz S, Milek S, Fuhrer F et al (2009) Region C of the Escherichia coli heat shock sigma factor RpoH (sigma 32) contains a turnover element for proteolysis by the FtsH protease. FEMS Microbiol Lett 290(2):199–208
Obrist M, Milek S, Klauck E, Hengge R (2007) Region 2.1 of the Escherichia coli heat-shock sigma factor RpoH (sigma32) is necessary but not sufficient for degradation by the FtsH protease. Microbiology 153(8):2560–2571
Obrist M, Narberhaus F (2005) Identification of a turnover element in region 2.1 of Escherichia coli sigma32 by a bacterial one-hybrid approach. J Bacteriol 187(11):3807–3813
Rodriguez F, Arsene-Ploetze F, Rist W, Rudiger S et al (2008) Molecular basis for regulation of the heat shock transcription factor sigma32 by the DnaK and DnaJ chaperones. Mol Cell 32(3):347–358
Okuno T, Yamada-Inagawa T, Karata K, Yamanaka K et al (2004) Spectrometric analysis of degradation of a physiological substrate sigma32 by Escherichia coli AAA protease FtsH. J Struct Biol 146(1–2):148–154
Karzai AW, Roche ED, Sauer RT (2000) The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue. Nat Struct Biol 7(6):449–455
Lies M, Maurizi MR (2008) Turnover of endogenous SsrA-tagged proteins mediated by ATP-dependent proteases in Escherichia coli. J Biol Chem 283(34):22918–22929
Gur E, Ottofuelling R, Dougan DA (2013) Machines of destruction – AAA+ proteases and the adaptors that control them. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:3–33
Herman C, Thevenet D, Bouloc P, Walker GC et al (1998) Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH). Genes Dev 12(9):1348–1355
Akiyama Y, Kihara A, Ito K (1996) Subunit a of proton ATPase F0 sector is a substrate of the FtsH protease in Escherichia coli. FEBS Lett 399(1–2):26–28
Akiyama Y, Kihara A, Tokuda H, Ito K (1996) FtsH (HflB) is an ATP-dependent protease selectively acting on SecY and some other membrane proteins. J Biol Chem 271(49):31196–31201
van Stelten J, Silva F, Belin D, Silhavy TJ (2009) Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY. Science 325(5941):753–756
Chiba S, Akiyama Y, Ito K (2002) Membrane protein degradation by FtsH can be initiated from either end. J Bacteriol 184(17):4775–4782
Chiba S, Akiyama Y, Mori H, Matsuo E et al (2000) Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis. EMBO Rep 1(1):47–52
Kihara A, Akiyama Y, Ito K (1999) Dislocation of membrane proteins in FtsH-mediated proteolysis. EMBO J 18(11):2970–2981
Shimohata N, Chiba S, Saikawa N, Ito K et al (2002) The Cpx stress response system of Escherichia coli senses plasma membrane proteins and controls HtpX, a membrane protease with a cytosolic active site. Genes Cells 7(7):653–662
Akiyama Y (2009) Quality control of cytoplasmic membrane proteins in Escherichia coli. J Biochem 146(4):449–454
Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007) Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 76:295–329
Zhang YM, Rock CO (2008) Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 6(3):222–233
Anderson MS, Bull HG, Galloway SM, Kelly TM et al (1993) UDP-N-acetylglucosamine acyltransferase of Escherichia coli. The first step of endotoxin biosynthesis is thermodynamically unfavorable. J Biol Chem 268(26):19858–19865
Santos D, De Almeida DF (1975) Isolation and characterization of a new temperature-sensitive cell division mutant of Escherichia coli K-12. J Bacteriol 124(3):1502–1507
Begg KJ, Tomoyasu T, Donachie WD, Khattar M et al (1992) Escherichia coli mutant Y16 is a double mutant carrying thermosensitive ftsH and ftsI mutations. J Bacteriol 174(7):2416–2417
Qu JN, Makino SI, Adachi H, Koyama Y et al (1996) The tolZ gene of Escherichia coli is identified as the ftsH gene. J Bacteriol 178(12):3457–3461
Ogura T, Inoue K, Tatsuta T, Suzaki T et al (1999) Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli. Mol Microbiol 31(3):833–844
Fuhrer F, Langklotz S, Narberhaus F (2006) The C-terminal end of LpxC is required for degradation by the FtsH protease. Mol Microbiol 59(3):1025–1036
Fuhrer F, Muller A, Baumann H, Langklotz S et al (2007) Sequence and length recognition of the C-terminal turnover element of LpxC, a soluble substrate of the membrane-bound FtsH protease. J Mol Biol 372(2):485–496
Langklotz S, Schakermann M, Narberhaus F (2011) Control of lipopolysaccharide biosynthesis by FtsH-mediated proteolysis of LpxC is conserved in enterobacteria but not in all gram-negative bacteria. J Bacteriol 193(5):1090–1097
Katz C, Ron EZ (2008) Dual role of FtsH in regulating lipopolysaccharide biosynthesis in Escherichia coli. J Bacteriol 190(21):7117–7122
Pierson TM, Adams D, Bonn F, Martinelli P et al (2011) Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. PLoS Genet 7(10):e1002325
Tamura Y, Endo T, Iijima M, Sesaki H (2009) Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J Cell Biol 185(6):1029–1045
Potting C, Wilmes C, Engmann T, Osman C et al (2010) Regulation of mitochondrial phospholipids by Ups1/PRELI-like proteins depends on proteolysis and Mdm35. EMBO J 29(17):2888–2898
Osman C, Haag M, Potting C, Rodenfels J et al (2009) The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria. J Cell Biol 184(4):583–596
Tamura Y, Iijima M, Sesaki H (2010) Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J 29(17):2875–2887
Herman C, Prakash S, Lu CZ, Matouschek A et al (2003) Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH. Mol Cell 11(3):659–669
Koodathingal P, Jaffe NE, Kraut DA, Prakash S et al (2009) ATP-dependent proteases differ substantially in their ability to unfold globular proteins. J Biol Chem 284(28):18674–18684
Cascales E, Buchanan SK, Duche D, Kleanthous C et al (2007) Colicin biology. Microbiol Mol Biol Rev 71(1):158–229
Kleanthous C (2010) Swimming against the tide: progress and challenges in our understanding of colicin translocation. Nat Rev Microbiol 8(12):843–848
Walker D, Mosbahi K, Vankemmelbeke M, James R et al (2007) The role of electrostatics in colicin nuclease domain translocation into bacterial cells. J Biol Chem 282(43):31389–31397
Chauleau M, Mora L, Serba J, de Zamaroczy M (2011) FtsH-dependent processing of RNase colicins D and E3 means that only the cytotoxic domains are imported into the cytoplasm. J Biol Chem 286(33):29397–29407
Akiyama Y (1999) Self-processing of FtsH and its implication for the cleavage specificity of this protease. Biochemistry 38(36):11693–11699
Voos W, Ward LA, Truscott KN (2013) The role of AAA+ proteases in mitochondrial protein biogensis, homeostasis and activity control. In: Dougan DA (ed) Regulated proteolysis in microorganisms. Springer, Subcell Biochem 66:223–263
Okuno T, Yamanaka K, Ogura T (2006) An AAA protease FtsH can initiate proteolysis from internal sites of a model substrate, apo-flavodoxin. Genes Cells 11(3):261–268
Ayuso-Tejedor S, Nishikori S, Okuno T, Ogura T et al (2010) FtsH cleavage of non-native conformations of proteins. J Struct Biol 171(2):117–124
Koppen M, Langer T (2007) Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases. Crit Rev Biochem Mol Biol 42(3):221–242
Martinelli P, Rugarli EI (2010) Emerging roles of mitochondrial proteases in neurodegeneration. Biochim Biophys Acta 1797(1):1–10
Bonn F, Tatsuta T, Petrungaro C, Riemer J et al (2011) Presequence-dependent folding ensures MrpL32 processing by the m-AAA protease in mitochondria. EMBO J 30(13):2545–2556
Koppen M, Bonn F, Ehses S, Langer T (2009) Autocatalytic processing of m-AAA protease subunits in mitochondria. Mol Biol Cell 20(19):4216–4224
Di Bella D, Lazzaro F, Brusco A, Plumari M et al (2010) Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet 42(4):313–321
Casari G, De Fusco M, Ciarmatori S, Zeviani M et al (1998) Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93(6):973–983
Tatsuta T, Augustin S, Nolden M, Friedrichs B (2007) m-AAA protease-driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria. EMBO J 26(2):325–335
Ehses S, Raschke I, Mancuso G, Bernacchia A et al (2009) Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol 187(7):1023–1036
Ishihara N, Fujita Y, Oka T, Mihara K (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J 25(13):2966–2977
Lopez D, Vlamakis H, Kolter R (2010) Biofilms. Cold Spring Harb Perspect Biol 2(7):a98
McDougald D, Rice SA, Barraud N, Steinberg PD et al (2012) Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal. Nat Rev Microbiol 10(1):39–50
Bove P, Capozzi V, Garofalo C, Rieu A et al (2012) Inactivation of the ftsH gene of Lactobacillus plantarum WCFS1: effects on growth, stress tolerance, cell surface properties and biofilm formation. Microbiol Res 167(4):187–193
Simionato MR, Tucker CM, Kuboniwa M, Lamont G et al (2006) Porphyromonas gingivalis genes involved in community development with Streptococcus gordonii. Infect Immun 74(11):6419–6428
Herman C, Ogura T, Tomoyasu T, Hiraga S et al (1993) Cell growth and lambda phage development controlled by the same essential Escherichia coli gene, ftsH/hflB. Proc Natl Acad Sci U S A 90(22):10861–10865
Herman C, Thevenet D, D’Ari R, Bouloc P (1997) The HflB protease of Escherichia coli degrades its inhibitor lambda cIII. J Bacteriol 179(2):358–363
Kobiler O, Rokney A, Oppenheim AB (2007) Phage lambda CIII: a protease inhibitor regulating the lysis-lysogeny decision. PLoS One 2(4):e363
Saikawa N, Akiyama Y, Ito K (2004) FtsH exists as an exceptionally large complex containing HflKC in the plasma membrane of Escherichia coli. J Struct Biol 146(1–2):123–129
Bandyopadhyay K, Parua PK, Datta AB, Parrack P (2010) Escherichia coli HflK and HflC can individually inhibit the HflB (FtsH)-mediated proteolysis of lambdaCII in vitro. Arch Biochem Biophys 501(2):239–243
Kihara A, Akiyama Y, Ito K (1997) Host regulation of lysogenic decision in bacteriophage lambda: transmembrane modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA). Proc Natl Acad Sci U S A 94(11):5544–5549
Kihara A, Akiyama Y, Ito K (1998) Different pathways for protein degradation by the FtsH/HflKC membrane-embedded protease complex: an implication from the interference by a mutant form of a new substrate protein, YccA. J Mol Biol 279(1):175–188
Artal-Sanz M, Tavernarakis N (2009) Prohibitin and mitochondrial biology. Trends Endocrinol Metab 20(8):394–401
Merkwirth C, Langer T (2009) Prohibitin function within mitochondria: essential roles for cell proliferation and cristae morphogenesis. Biochim Biophys Acta 1793(1):27–32
Osman C, Merkwirth C, Langer T (2009) Prohibitins and the functional compartmentalization of mitochondrial membranes. J Cell Sci 122(Pt 21):3823–3830
Piechota J, Kolodziejczak M, Juszczak I, Sakamoto W et al (2010) Identification and characterization of high molecular weight complexes formed by matrix AAA proteases and prohibitins in mitochondria of Arabidopsis thaliana. J Biol Chem 285(17):12512–12521
Acknowledgements
We are grateful to Yoshinori Akiyama for stimulating discussion and invaluable comments and to David Dougan for generous editorial suggestions to the manuscript. We also thank to Chiyome Ichinose for secretarial assistant. This work was supported in part by grants from the Ministry of Education, Culture, Science, Sports and Technology of Japan.
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Okuno, T., Ogura, T. (2013). FtsH Protease-Mediated Regulation of Various Cellular Functions. In: Dougan, D. (eds) Regulated Proteolysis in Microorganisms. Subcellular Biochemistry, vol 66. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5940-4_3
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