Skip to main content
Log in

Targeting mitochondria: how intravacuolar bacterial pathogens manipulate mitochondria

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Manipulation of host cell function by bacterial pathogens is paramount for successful invasion and creation of a niche conducive to bacterial replication. Mitochondria play a role in many important cellular processes including energy production, cellular calcium homeostasis, lipid metabolism, haeme biosynthesis, immune signalling and apoptosis. The sophisticated integration of host cell processes by the mitochondrion have seen it emerge as a key target during bacterial infection of human host cells. This review highlights the targeting and interaction of this dynamic organelle by intravacuolar bacterial pathogens and the way that the modulation of mitochondrial function might contribute to pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abarca-Rojano E, Rosas-Medina P, Zamudio-Cortez P, Mondragon-Flores R, Sanchez-Garcia FJ (2003) Mycobacterium tuberculosis virulence correlates with mitochondrial cytochrome c release in infected macrophages. Scand J Immunol 58:419–427

    Article  CAS  PubMed  Google Scholar 

  • Abu-Hamad S, Arbel N, Calo D, Arzoine L, Israelson A, Keinan N, Ben-Romano R, Friedman O, Shoshan-Barmatz V (2009) The VDAC1 N-terminus is essential both for apoptosis and the protective effect of anti-apoptotic proteins. J Cell Sci 122:1906–1916

    Article  CAS  PubMed  Google Scholar 

  • Akgul C, Moulding DA, Edwards SW (2001) Molecular control of neutrophil apoptosis. FEBS Lett 487:318–322

    Article  CAS  PubMed  Google Scholar 

  • Aktories K (2011) Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol 9:487–498

    Article  CAS  PubMed  Google Scholar 

  • Alix E, Mukherjee S, Roy CR (2011) Subversion of membrane transport pathways by vacuolar pathogens. J Cell Biol 195:943–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arnoult D, Soares F, Tattoli I, Girardin SE (2011) Mitochondria in innate immunity. EMBO Rep 12:901–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arzoine L, Zilberberg N, Ben-Romano R, Shoshan-Barmatz V (2009) Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity. J Biol Chem 284:3946–3955

    Article  CAS  PubMed  Google Scholar 

  • Baker MJ, Palmer CS, Stojanovski D (2014) Mitochondrial protein quality control in health and disease. Br J Pharmacol 171:1870–1889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bastidas RJ, Valdivia RH (2016) Emancipating chlamydia: advances in the genetic manipulation of a recalcitrant intracellular pathogen. Microbiol Mol Biol Rev 80:411–427

    Article  PubMed  Google Scholar 

  • Beare PA, Larson CL, Gilk SD, Heinzen RA (2012) Two systems for targeted gene deletion in Coxiella burnetii. Appl Environ Microbiol 78:4580–4589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brenner DJ, Steigerwalt AG, McDade JE (1979) Classification of the Legionnaires’ disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legionellaceae, familia nova. Ann Intern Med 90:656–658

    Article  CAS  PubMed  Google Scholar 

  • Cadieux N, Parra M, Cohen H, Maric D, Morris SL, Brennan MJ (2011) Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein. Microbiology 157:793–804

    Article  CAS  PubMed  Google Scholar 

  • Carey KL, Newton HJ, Luhrmann A, Roy CR (2011) The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication. PLoS Pathog 7:e1002056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chacinska A, Lind M, Frazier AE, Dudek J, Meisinger C, Geissler A, Sickmann A, Meyer HE, Truscott KN, Guiard B, Pfanner N, Rehling P (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120:817–829

    Article  CAS  PubMed  Google Scholar 

  • Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N (2009) Importing mitochondrial proteins: machineries and mechanisms. Cell 138:628–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chacinska A, van der Laan M, Mehnert CS, Guiard B, Mick DU, Hutu DP, Truscott KN, Wiedemann N, Meisinger C, Pfanner N, Rehling P (2010) Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting. Mol Cell Biol 30:307–318

    Article  CAS  PubMed  Google Scholar 

  • Chan NC, Lithgow T (2008) The peripheral membrane subunits of the SAM complex function codependently in mitochondrial outer membrane biogenesis. Mol Biol Cell 19:126–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandran Darbari V, Waksman G (2015) Structural biology of bacterial type IV secretion systems. Annu Rev Biochem 84:603–629

    Article  CAS  PubMed  Google Scholar 

  • Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301:513–517

    Article  CAS  PubMed  Google Scholar 

  • Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G (2015) Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol 13:343–359

    Article  CAS  PubMed  Google Scholar 

  • Creasey EA, Isberg RR (2014) Maintenance of vacuole integrity by bacterial pathogens. Curr Opin Microbiol 17:46–52

    Article  CAS  PubMed  Google Scholar 

  • Cunha LD, Ribeiro JM, Fernandes TD, Massis LM, Khoo CA, Moffatt JH, Newton HJ, Roy CR, Zamboni DS (2015) Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA. Nat Commun 6:10205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curran SP, Leuenberger D, Oppliger W, Koehler CM (2002) The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier. EMBO J 21:942–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Stefani D, Bononi A, Romagnoli A, Messina A, De Pinto V, Pinton P, Rizzuto R (2012) VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria. Cell Death Differ 19:267–273

    Article  PubMed  CAS  Google Scholar 

  • Derre I, Pypaert M, Dautry-Varsat A, Agaisse H (2007) RNAi screen in Drosophila cells reveals the involvement of the Tom complex in Chlamydia infection. PLoS Pathog 3:1446–1458

    Article  CAS  PubMed  Google Scholar 

  • Diepold A, Armitage JP (2015) Type III secretion systems: the bacterial flagellum and the injectisome. Philos Trans R Soc Lond B Biol Sci 370:20150020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dolezal P, Likic V, Tachezy J, Lithgow T (2006) Evolution of the molecular machines for protein import into mitochondria. Science 313:314–318

    Article  CAS  PubMed  Google Scholar 

  • Dolezal P, Aili M, Tong J, Jiang JH, Marobbio CM, Lee SF, Schuelein R, Belluzzo S, Binova E, Mousnier A, Frankel G, Giannuzzi G, Palmieri F, Gabriel K, Naderer T, Hartland EL, Lithgow T (2012) Legionella pneumophila secretes a mitochondrial carrier protein during infection. PLoS Pathog 8:e1002459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eckart RA, Bisle S, Schulze-Luehrmann J, Wittmann I, Jantsch J, Schmid B, Berens C, Luhrmann A (2014) Antiapoptotic activity of Coxiella burnetii effector protein AnkG is controlled by p32-dependent trafficking. Infect Immun 82:2763–2771

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Escoll P, Mondino S, Rolando M, Buchrieser C (2016) Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy. Nat Rev Microbiol 14:5–19

    Article  CAS  PubMed  Google Scholar 

  • Fuchs TM, Eisenreich W, Heesemann J, Goebel W (2012) Metabolic adaptation of human pathogenic and related nonpathogenic bacteria to extra- and intracellular habitats. FEMS Microbiol Rev 36:435–462

    Article  CAS  PubMed  Google Scholar 

  • Galan JE, Lara-Tejero M, Marlovits TC, Wagner S (2014) Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 68:415–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganeshan K, Chawla A (2014) Metabolic regulation of immune responses. Annu Rev Immunol 32:609–634

    Article  CAS  PubMed  Google Scholar 

  • Gillies LA, Kuwana T (2014) Apoptosis regulation at the mitochondrial outer membrane. J Cell Biochem 115:632–640

    Article  CAS  PubMed  Google Scholar 

  • Gold V, Kudryashev M (2016) Recent progress in structure and dynamics of dual-membrane-spanning bacterial nanomachines. Curr Opin Struct Biol 39:1–7

    Article  CAS  PubMed  Google Scholar 

  • Gray MW, Burger G, Lang BF (1999) Mitochondrial evolution. Science 283:1476–1481

    Article  CAS  PubMed  Google Scholar 

  • Green ER, Mecsas J (2016) Bacterial secretion systems: an overview. Microbiol Spectr 4:10.1128/microbiolspec.VMBF-0012-2015

  • Guiney DG (2005) The role of host cell death in Salmonella infections. Curr Top Microbiol Immunol 289:131–150

    CAS  PubMed  Google Scholar 

  • Ham H, Sreelatha A, Orth K (2011) Manipulation of host membranes by bacterial effectors. Nat Rev Microbiol 9:635–646

    Article  CAS  PubMed  Google Scholar 

  • Harbauer AB, Zahedi RP, Sickmann A, Pfanner N, Meisinger C (2014) The protein import machinery of mitochondria—a regulatory hub in metabolism, stress, and disease. Cell Metab 19:357–372

    Article  CAS  PubMed  Google Scholar 

  • Hernandez LD, Pypaert M, Flavell RA, Galan JE (2003) A Salmonella protein causes macrophage cell death by inducing autophagy. J Cell Biol 163:1123–1131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herweg JA, Rudel T (2016) Interaction of Chlamydiae with human macrophages. FEBS J 283:608–618

    Article  CAS  PubMed  Google Scholar 

  • Ho BT, Dong TG, Mekalanos JJ (2014) A view to a kill: the bacterial type VI secretion system. Cell Host Microbe 15:9–21

    Article  CAS  PubMed  Google Scholar 

  • Hohr AI, Straub SP, Warscheid B, Becker T, Wiedemann N (2015) Assembly of beta-barrel proteins in the mitochondrial outer membrane. Biochim Biophys Acta 1853:74–88

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1983) Formation of a novel phagosome by the Legionnaires’ disease bacterium (Legionella pneumophila) in human monocytes. J Exp Med 158:1319–1331

    Article  CAS  PubMed  Google Scholar 

  • Horwitz MA, Maxfield FR (1984) Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J Cell Biol 99:1936–1943

    Article  CAS  PubMed  Google Scholar 

  • Houben EN, Korotkov KV, Bitter W (2014) Take five—type VII secretion systems of Mycobacteria. Biochim Biophys Acta 1843:1707–1716

    Article  CAS  PubMed  Google Scholar 

  • Jamwal S, Midha MK, Verma HN, Basu A, Rao KV, Manivel V (2013) Characterizing virulence-specific perturbations in the mitochondrial function of macrophages infected with Mycobacterium tuberculosis. Sci Rep 3:1328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jiang JH, Davies JK, Lithgow T, Strugnell RA, Gabriel K (2011) Targeting of Neisserial PorB to the mitochondrial outer membrane: an insight on the evolution of beta-barrel protein assembly machines. Mol Microbiol 82:976–987

    Article  CAS  PubMed  Google Scholar 

  • Jiang JH, Tong J, Gabriel K (2012a) Hijacking mitochondria: bacterial toxins that modulate mitochondrial function. IUBMB Life 64:397–401

    Article  CAS  PubMed  Google Scholar 

  • Jiang JH, Tong J, Tan KS, Gabriel K (2012b) From evolution to pathogenesis: the link between beta-barrel assembly machineries in the outer membrane of mitochondria and gram-negative bacteria. Int J Mol Sci 13:8038–8050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasahara A, Scorrano L (2014) Mitochondria: from cell death executioners to regulators of cell differentiation. Trends Cell Biol 24:761–770

    Article  CAS  PubMed  Google Scholar 

  • Keinan N, Pahima H, Ben-Hail D, Shoshan-Barmatz V (2013) The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis. Biochim Biophys Acta 1833:1745–1754

    Article  CAS  PubMed  Google Scholar 

  • Kispal G, Csere P, Prohl C, Lill R (1999) The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. EMBO J 18:3981–3989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klingenbeck L, Eckart RA, Berens C, Luhrmann A (2013) The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic apoptosis at the mitochondrial level. Cell Microbiol 15:675–687

    Article  CAS  PubMed  Google Scholar 

  • Knittler MR, Sachse K (2015) Chlamydia psittaci: update on an underestimated zoonotic agent. Pathog Dis 73:1–15

    PubMed  Google Scholar 

  • Kutik S, Stojanovski D, Becker L, Becker T, Meinecke M, Kruger V, Prinz C, Meisinger C, Guiard B, Wagner R, Pfanner N, Wiedemann N (2008) Dissecting membrane insertion of mitochondrial beta-barrel proteins. Cell 132:1011–1024

    Article  CAS  PubMed  Google Scholar 

  • La Rovere RM, Roest G, Bultynck G, Parys JB (2016) Intracellular Ca signaling and Ca microdomains in the control of cell survival, apoptosis and autophagy. Cell Calcium 2016:S0143-4160(16)30048-3

    Google Scholar 

  • Lazarou M, Stojanovski D, Frazier AE, Kotevski A, Dewson G, Craigen WJ, Kluck RM, Vaux DL, Ryan MT (2010) Inhibition of Bak activation by VDAC2 is dependent on the Bak transmembrane anchor. J Biol Chem 285:36876–36883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lill R (2009) Function and biogenesis of iron-sulphur proteins. Nature 460:831–838

    Article  CAS  PubMed  Google Scholar 

  • Lobet E, Letesson JJ, Arnould T (2015) Mitochondria: a target for bacteria. Biochem Pharmacol 94:173–185

    Article  CAS  PubMed  Google Scholar 

  • Lucattini R, Likic VA, Lithgow T (2004) Bacterial proteins predisposed for targeting to mitochondria. Mol Biol Evol 21:652–658

    Article  CAS  PubMed  Google Scholar 

  • Luhrmann A, Roy CR (2007) Coxiella burnetii inhibits activation of host cell apoptosis through a mechanism that involves preventing cytochrome c release from mitochondria. Infect Immun 75:5282–5289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luhrmann A, Nogueira CV, Carey KL, Roy CR (2010) Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proc Natl Acad Sci U S A 107:18997–19001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Margulis L (1970) Origin of eukaryotic cells; evidence and research implications for a theory of the origin and evolution of microbial, plant, and animal cells on the Precambrian earth. Yale University Press, New Haven

    Google Scholar 

  • Martin LA, Kennedy BE, Karten B (2016) Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function. J Bioenerg Biomembr 48:137–151

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto A (1981) Isolation and electron microscopic observations of intracytoplasmic inclusions containing Chlamydia psittaci. J Bacteriol 145:605–612

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumoto A, Bessho H, Uehira K, Suda T (1991) Morphological studies of the association of mitochondria with chlamydial inclusions and the fusion of chlamydial inclusions. J Electron Microsc (Tokyo) 40:356–363

    CAS  Google Scholar 

  • McDonough JA, Newton HJ, Klum S, Swiss R, Agaisse H, Roy CR (2013) Host pathways important for Coxiella burnetii infection revealed by genome-wide RNA interference screening. MBio 4:e00606–e00612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehlitz A, Karunakaran K, Herweg JA, Krohne G, van de Linde S, Rieck E, Sauer M, Rudel T (2014) The chlamydial organism Simkania negevensis forms ER vacuole contact sites and inhibits ER-stress. Cell Microbiol 16:1224–1243

    Article  CAS  PubMed  Google Scholar 

  • Mirrashidi KM, Elwell CA, Verschueren E, Johnson JR, Frando A, Von Dollen J, Rosenberg O, Gulbahce N, Jang G, Johnson T, Jager S, Gopalakrishnan AM, Sherry J, Dunn JD, Olive A, Penn B, Shales M, Cox JS, Starnbach MN, Derre I, Valdivia R, Krogan NJ, Engel J (2015) Global mapping of the inc-human interactome reveals that retromer restricts chlamydia infection. Cell Host Microbe 18:109–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moffatt JH, Newton P, Newton HJ (2015) Coxiella burnetii: turning hostility into a home. Cell Microbiol 17:621–631

    Article  CAS  PubMed  Google Scholar 

  • Morlino G, Barreiro O, Baixauli F, Robles-Valero J, Gonzalez-Granado JM, Villa-Bellosta R, Cuenca J, Sanchez-Sorzano CO, Veiga E, Martin-Cofreces NB, Sanchez-Madrid F (2014) Miro-1 links mitochondria and microtubule Dynein motors to control lymphocyte migration and polarity. Mol Cell Biol 34:1412–1426

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mossmann D, Meisinger C, Vogtle FN (2012) Processing of mitochondrial presequences. Biochim Biophys Acta 1819:1098–1106

    Article  CAS  PubMed  Google Scholar 

  • Mueller KE, Wolf K, Fields KA (2016) Gene deletion by fluorescence-reported allelic exchange mutagenesis in Chlamydia trachomatis. MBio 7:e01817–01815

    Article  PubMed  PubMed Central  Google Scholar 

  • Muller A, Gunther D, Brinkmann V, Hurwitz R, Meyer TF, Rudel T (2000) Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells. EMBO J 19:5332–5343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muller A, Rassow J, Grimm J, Machuy N, Meyer TF, Rudel T (2002) VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial import pathways. EMBO J 21:1916–1929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagai H, Kubori T (2011) Type IVB secretion systems of legionella and other gram-negative bacteria. Front Microbiol 2:136

    Article  PubMed  PubMed Central  Google Scholar 

  • Nagai H, Cambronne ED, Kagan JC, Amor JC, Kahn RA, Roy CR (2005) A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc Natl Acad Sci U S A 102:826–831

    Article  CAS  PubMed  Google Scholar 

  • Neupert W, Herrmann JM (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723–749

    Article  CAS  PubMed  Google Scholar 

  • Niu H, Yamaguchi M, Rikihisa Y (2008) Subversion of cellular autophagy by Anaplasma phagocytophilum. Cell Microbiol 10:593–605

    Article  CAS  PubMed  Google Scholar 

  • Niu H, Kozjak-Pavlovic V, Rudel T, Rikihisa Y (2010) Anaplasma phagocytophilum Ats-1 is imported into host cell mitochondria and interferes with apoptosis induction. PLoS Pathog 6:e1000774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Noriea NF, Clark TR, Hackstadt T (2015) Targeted knockout of the Rickettsia rickettsii OmpA surface antigen does not diminish virulence in a mammalian model system. MBio 6:e00323-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Omsland A, Heinzen RA (2011) Life on the outside: the rescue of Coxiella burnetii from its host cell. Annu Rev Microbiol 65:111–128

    Article  CAS  PubMed  Google Scholar 

  • Palucci I, Camassa S, Cascioferro A, Sali M, Anoosheh S, Zumbo A, Minerva M, Iantomasi R, De Maio F, Di Sante G, Ria F, Sanguinetti M, Palu G, Brennan MJ, Manganelli R, Delogu G (2016) PE_PGRS33 contributes to Mycobacterium tuberculosis entry in macrophages through interaction with TLR2. PLoS One 11:e0150800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park JS, Tamayo MH, Gonzalez-Juarrero M, Orme IM, Ordway DJ (2006) Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages. J Leukoc Biol 79:80–86

    Article  CAS  PubMed  Google Scholar 

  • Pernas L, Scorrano L (2016) Mito-morphosis: mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function. Annu Rev Physiol 78:505–531

    Article  CAS  PubMed  Google Scholar 

  • Phillips MJ, Voeltz GK (2016) Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol 17:69–82

    Article  CAS  PubMed  Google Scholar 

  • Portaliou AG, Tsolis KC, Loos MS, Zorzini V, Economou A (2016) Type III secretion: building and operating a remarkable nanomachine. Trends Biochem Sci 41:175–189

    Article  CAS  PubMed  Google Scholar 

  • Raturi A, Simmen T (2013) Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM). Biochim Biophys Acta 1833:213–224

    Article  CAS  PubMed  Google Scholar 

  • Rehling P, Model K, Brandner K, Kovermann P, Sickmann A, Meyer HE, Kuhlbrandt W, Wagner R, Truscott KN, Pfanner N (2003) Protein insertion into the mitochondrial inner membrane by a twin-pore translocase. Science 299:1747–1751

    Article  CAS  PubMed  Google Scholar 

  • Reis K, Fransson A, Aspenstrom P (2009) The Miro GTPases: at the heart of the mitochondrial transport machinery. FEBS Lett 583:1391–1398

    Article  CAS  PubMed  Google Scholar 

  • Rizzuto R, Brini M, Murgia M, Pozzan T (1993) Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science 262:744–747

    Article  CAS  PubMed  Google Scholar 

  • Robert V, Volokhina EB, Senf F, Bos MP, Van Gelder P, Tommassen J (2006) Assembly factor Omp85 recognizes its outer membrane protein substrates by a species-specific C-terminal motif. PLoS Biol 4:e377

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rudel T, Kepp O, Kozjak-Pavlovic V (2010) Interactions between bacterial pathogens and mitochondrial cell death pathways. Nat Rev Microbiol 8:693–705

    Article  CAS  PubMed  Google Scholar 

  • Schatz G, Dobberstein B (1996) Common principles of protein translocation across membranes. Science 271:1519–1526

    Article  CAS  PubMed  Google Scholar 

  • Schlesinger LS (1996) Entry of Mycobacterium tuberculosis into mononuclear phagocytes. Curr Top Microbiol Immunol 215:71–96

    CAS  PubMed  Google Scholar 

  • Schmidt O, Pfanner N, Meisinger C (2010) Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol 11:655–667

    Article  CAS  PubMed  Google Scholar 

  • Schulz C, Lytovchenko O, Melin J, Chacinska A, Guiard B, Neumann P, Ficner R, Jahn O, Schmidt B, Rehling P (2011) Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex. J Cell Biol 195:643–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinzel M, Tan T, Wendling P, Kalbacher H, Ozbalci C, Chelius X, Westermann B, Brugger B, Rapaport D, Dimmer KS (2016) Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP-dependent biogenesis pathway. EMBO Rep 17:965–981

    Article  CAS  PubMed  Google Scholar 

  • Song J, Tamura Y, Yoshihisa T, Endo T (2014) A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex. EMBO Rep 15:670–677

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stavru F, Palmer AE, Wang C, Youle RJ, Cossart P (2013) Atypical mitochondrial fission upon bacterial infection. Proc Natl Acad Sci U S A 110:16003–16008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stojanovski D, Bohnert M, Pfanner N, van der Laan M (2012) Mechanisms of protein sorting in mitochondria. Cold Spring Harb Perspect Biol 4:a011320

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sukumaran SK, Fu NY, Tin CB, Wan KF, Lee SS, Yu VC (2010) A soluble form of the pilus protein FimA targets the VDAC-hexokinase complex at mitochondria to suppress host cell apoptosis. Mol Cell 37:768–783

    Article  CAS  PubMed  Google Scholar 

  • Suzuki M, Danilchanka O, Mekalanos JJ (2014) Vibrio cholerae T3SS effector VopE modulates mitochondrial dynamics and innate immune signaling by targeting Miro GTPases. Cell Host Microbe 16:581–591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    Article  CAS  PubMed  Google Scholar 

  • Tatsuta T, Scharwey M, Langer T (2014) Mitochondrial lipid trafficking. Trends Cell Biol 24:44–52

    Article  CAS  PubMed  Google Scholar 

  • van der Laan M, Wiedemann N, Mick DU, Guiard B, Rehling P, Pfanner N (2006) A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria. Curr Biol 16:2271–2276

    Article  PubMed  CAS  Google Scholar 

  • van der Laan M, Meinecke M, Dudek J, Hutu DP, Lind M, Perschil I, Guiard B, Wagner R, Pfanner N, Rehling P (2007) Motor-free mitochondrial presequence translocase drives membrane integration of preproteins. Nat Cell Biol 9:1152–1159

    Article  PubMed  CAS  Google Scholar 

  • van der Laan M, Hutu DP, Rehling P (2010) On the mechanism of preprotein import by the mitochondrial presequence translocase. Biochim Biophys Acta 1803:732–739

    Article  PubMed  CAS  Google Scholar 

  • Vance JE (2014) MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim Biophys Acta 1841:595–609

    Article  CAS  PubMed  Google Scholar 

  • Vance JE (2015) Phospholipid synthesis and transport in mammalian cells. Traffic 16:1–18

    Article  CAS  PubMed  Google Scholar 

  • Vaux DL (2011) Apoptogenic factors released from mitochondria. Biochim Biophys Acta 1813:546–550

    Article  CAS  PubMed  Google Scholar 

  • Vazquez CL, Colombo MI (2010) Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection. Cell Death Differ 17:421–438

    Article  CAS  PubMed  Google Scholar 

  • van Vliet AR, Verfaillie T, Agostinis P (2014) New functions of mitochondria associated membranes in cellular signaling. Biochim Biophys Acta 1843:2253–2262

    Article  PubMed  CAS  Google Scholar 

  • Voth DE, Howe D, Beare PA, Vogel JP, Unsworth N, Samuel JE, Heinzen RA (2009) The Coxiella burnetii ankyrin repeat domain-containing protein family is heterogeneous, with C-terminal truncations that influence Dot/Icm-mediated secretion. J Bacteriol 191:4232–4242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voth DE, Beare PA, Howe D, Sharma UM, Samoilis G, Cockrell DC, Omsland A, Heinzen RA (2011) The Coxiella burnetii cryptic plasmid is enriched in genes encoding type IV secretion system substrates. J Bacteriol 193:1493–1503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walther DM, Papic D, Bos MP, Tommassen J, Rapaport D (2009a) Signals in bacterial beta-barrel proteins are functional in eukaryotic cells for targeting to and assembly in mitochondria. Proc Natl Acad Sci U S A 106:2531–2536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walther DM, Rapaport D, Tommassen J (2009b) Biogenesis of beta-barrel membrane proteins in bacteria and eukaryotes: evolutionary conservation and divergence. Cell Mol Life Sci 66:2789–2804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Webb CT, Gorman MA, Lazarou M, Ryan MT, Gulbis JM (2006) Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol Cell 21:123–133

    Article  CAS  PubMed  Google Scholar 

  • Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V (2014) Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction. Biochim Biophys Acta 1843:2270–2281

    Article  CAS  PubMed  Google Scholar 

  • Wenz LS, Opalinski L, Schuler MH, Ellenrieder L, Ieva R, Bottinger L, Qiu J, van der Laan M, Wiedemann N, Guiard B, Pfanner N, Becker T (2014) The presequence pathway is involved in protein sorting to the mitochondrial outer membrane. EMBO Rep 15:678–685

    CAS  PubMed  PubMed Central  Google Scholar 

  • West AP, Brodsky IE, Rahner C, Woo DK, Erdjument-Bromage H, Tempst P, Walsh MC, Choi Y, Shadel GS, Ghosh S (2011a) TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472:476–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • West AP, Shadel GS, Ghosh S (2011b) Mitochondria in innate immune responses. Nat Rev Immunol 11:389–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiedemann N, Pfanner N, Ryan MT (2001) The three modules of ADP/ATP carrier cooperate in receptor recruitment and translocation into mitochondria. EMBO J 20:951–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiedemann N, Kozjak V, Chacinska A, Schonfisch B, Rospert S, Ryan MT, Pfanner N, Meisinger C (2003) Machinery for protein sorting and assembly in the mitochondrial outer membrane. Nature 424:565–571

    Article  CAS  PubMed  Google Scholar 

  • Wiedemann N, van der Laan M, Hutu DP, Rehling P, Pfanner N (2007) Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain. J Cell Biol 179:1115–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winchell CG, Steele S, Kawula T, Voth DE (2016) Dining in: intracellular bacterial pathogen interplay with autophagy. Curr Opin Microbiol 29:9–14

    Article  CAS  PubMed  Google Scholar 

  • Wyllie S, Ashley RH, Longbottom D, Herring AJ (1998) The major outer membrane protein of Chlamydia psittaci functions as a porin-like ion channel. Infect Immun 66:5202–5207

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Shao F (2015) The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus. Immunol Rev 265:85–102

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Zhu Y (2015) Diversity of bacterial manipulation of the host ubiquitin pathways. Cell Microbiol 17:26–34

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hayley J. Newton or Diana Stojanovski.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fielden, L.F., Kang, Y., Newton, H.J. et al. Targeting mitochondria: how intravacuolar bacterial pathogens manipulate mitochondria. Cell Tissue Res 367, 141–154 (2017). https://doi.org/10.1007/s00441-016-2475-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-016-2475-x

Keywords

Navigation