Abstract
Cardiolipin (CL) is a key player in bacterial cell biology. CL accumulates at the poles of rod-shaped cells; the polar localization and function of diverse bacterial proteins are CL-dependent. Cardiolipin (CL) is an unusual phospholipid comprised of a glycerol headgroup coupled with two phosphatidate moieties. CL-rich membrane domains are often visualized with the fluorescent indicator 10-N-nonyl-acridine orange (NAO). Recent data show that NAO can also indicate phosphatidylglycerol localization under different experimental conditions, in the absence of CL. The formation of CL-rich membrane domains at bacterial cell poles was predicted to occur spontaneously, by lipid microphase separation arising from the conical CL shape. New data reveal that membrane-anchored cardiolipin synthase A is targeted to the cytoplasmic membrane surface at bacterial cell poles. Thus, localized CL synthesis, interaction of CL with ClsA, and membrane curvature could all contribute to retention of CL at cell poles. These observations provide new insight regarding the mechanism for assembly of CL-rich membrane domains in prokaryotes and eukaryotes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Benesch MGK, Lewis RNAH., McElhaney RN (2015) On the miscibility of cardiolipin with 1,2-diacyl phosphoglycerides: binary mixtures of dimyristoylphosphatidylglycerol and tetramyristoylcardiolipin. Biochim Biophys Acta 1848:2878–2888. https://doi.org/10.1016/j.bbamem.2015.08.003
Boekema EJ, Scheffers DJ, van Bezouwen LS, Bolhuis H, Folea IM (2013) Focus on membrane differentiation and membrane domains in the prokaryotic cell. J Mol Microbiol Biotechnol 23:345–356. https://doi.org/10.1159/000351361
Busiek KK, Margolin W (2015) Bacterial actin and tubulin homologs in cell growth and division. Curr Biol 25:R243–R254. https://doi.org/10.1016/j.cub.2015.01.030
Frias M, Benesch MGK, Lewis RNAH., McElhaney RN (2011) On the miscibility of cardiolipin with 1,2-diacyl phosphoglycerides: Binary mixtures of dimyristoylphosphatidylethanolamine and tetramyristoylcardiolipin. Biochim Biophys Acta 1808:774–783. https://doi.org/10.1016/j.bbamem.2010.12.010
Huang KC, Mukhopadhyay R, Wingreen NS (2006) A curvature-mediated mechanism for localization of lipids to bacterial poles. PLoS Comput Biol 2:e151
Kawai F, Shoda M, Harashima R, Sadaie Y, Hara H, Matsumoto K (2004) Cardiolipin domains in Bacillus subtilis marburg membranes. J Bacteriol 186:1475–1483
Koppelman C-M, den Blaauwen T, Duursma MC, Heeren RMA, Nanninga N (2001) Escherichia coli minicell membranes are enriched in cardiolipin. J Bacteriol 183:6144–6147
Laloux G, Jacobs-Wagner C (2014) How do bacteria localize proteins to the cell pole? J Cell Sci 127:11–19. https://doi.org/10.1242/jcs.138628
Landgraf D, Okumus B, Chien P, Baker TA, Paulsson J (2013) Segregation of molecules at cell division reveals native protein localization. Nat Methods 9:480–486
Lewis RNAH., McElhaney RN (2000) Surface charge markedly attenuates the nonlamellar phase-forming propensities of lipid bilayer membranes: calorimetric and 31P-nuclear magnetic resonance studies of mixtures of cationic, anionic, and zwitterionic lipids. Biophys J 79:1455–1464. https://doi.org/10.1016/S0006-3495(00)76397-1
Lewis RNAH., McElhaney RN (2009) The physicochemical properties of cardiolipin bilayers and cardiolipin-containing lipid membranes. Biochim Biophys Acta 1788:2069–2079. https://doi.org/10.1016/j.bbamem.2009.03.014
Lin TY, Weibel DB (2016) Organization and function of anionic phospholipids in bacteria. Appl Microbiol Biotechnol 100:4255–4267. https://doi.org/10.1007/s00253-016-7468-x
Lutkenhaus J (2012) The ParA/MinD family puts things in their place. Trends Microbiol 20:411–418. https://doi.org/10.1016/j.tim.2012.05.002
Margolin W (2012) The price of tags in protein localization studies. J Bacteriol 194:6369–6371
Mileykovskaya E, Dowhan W (2000) Visualization of phospholipid domains in Escherichia coli by using the cardiolipin-specific fluorescent dye 10-N-nonyl acridine orange. J Bacteriol 182:1172–1175
Mileykovskaya E, Dowhan W (2009) Cardiolipin membrane domains in prokaryotes and eukaryotes. Biochim Biophys Acta 1788:2084–2091. https://doi.org/10.1016/j.bbamem.2009.04.003
Mileykovskaya E, Dowhan W, Birke RL, Zheng D, Lutterodt L, Haines TH (2001) Cardiolipin binds nonyl acridine orange by aggregating the dye at exposed hydrophobic domains on bilayer surfaces. FEBS Lett 507:187–190
Mukhopadhyay R, Huang KC, Wingreen NS (2008) Lipid localization in bacterial cells through curvature-mediated microphase separation. Biophys J 95:1034–1049
Oliver PM, Crooks JA, Leidl M, Yoon EJ, Saghatelian A, Weibel DB (2014) Localization of anionic phospholipids in Escherichia coli cells. J Bacteriol 196:3386–3398
Paintdakhi A, Parry BR, Campos M, Irnov I, Elf J, Surovtsev I, Jacobs-Wagner C (2016) Oufti: an integrated software package for high-accuracy high-throughput quantitative microscopy analysis. Mol Microbiol 99:767–777. https://doi.org/10.1111/mmi.13264
Petit JM, Maftah A, Ratinaud MH, Julien R (1992) 10N-nonyl acridine orange interacts with cardiolipin and allows the quantification of this phospholipid in isolated mitochondria. Eur J Biochem 209:267–273
Renner LD, Weibel DB (2011) Cardiolipin microdomains localize to negatively curved regions of Escherichia coli membranes. Proc Natl Acad Sci USA 108:6264–6269. https://doi.org/10.1073/pnas.1015757108
Romantsov T, Wood JM (2016) Contributions of membrane lipids to bacterial cell homeostasis upon osmotic challenge. In: Geiger O (ed) Biogenesis of fatty acids, lipids and membranes. Handbook of Hydrocarbon and Lipid Microbiology, 2 edn, vol 3. Springer science + business media, Heidelberg
Romantsov T, Helbig S, Culham DE, Gill C, Stalker L, Wood JM (2007) Cardiolipin promotes polar localization of osmosensory transporter ProP in Escherichia coli. Mol Microbiol 64:1455–1465
Romantsov T, Stalker L, Culham DE, Wood JM (2008) Cardiolipin controls the osmotic stress response and the subcellular location of transporter ProP in Escherichia coli. J Biol Chem 283:12314–12323
Romantsov T, Guan Z, Wood JM (2009) Cardiolipin and the osmotic stress responses of bacteria. Biochim Biophys Acta 1788:2092–2100
Romantsov T, Battle AR, Hendel JM, Martinac B, Wood JM (2010) Protein localization in Escherichia coli cells: comparison of cytoplasmic membrane proteins ProP, LacY, ProW, AqpZ, MscS, and MscL. J Bacteriol 192:912–924
Romantsov T et al. (2017) Cardiolipin synthase A colocalizes with cardiolipin and osmosensing transporter ProP at the poles of Escherichia coli cells Mol Microbiol. https://doi.org/10.1111/mmi.13904
Rudner DZ, Pan Q, Losick RM (2002) Evidence that subcellular localization of a bacterial membrane protein is achieved by diffusion and capture. Proc Nat Acad Sci USA 99:8701–8706. https://doi.org/10.1073/pnas.132235899
Shiomi D (2017) Polar localization of MreB actin is inhibited by anionic phospholipids in the rod-shaped bacterium Escherichia coli. Curr Genet 63:845–848. https://doi.org/10.1007/s00294-017-0696-5
Tan BK, Bogdanov M, Zhao J, Dowhan W, Raetz CRH, Guan Z (2012) Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates. Proc Natl Acad Sci USA 109:16504–16509
Tropp BE (1997) Cardiolipin synthase from Escherichia coli. Biochim Biophys Acta 1348:192–200
Vanounou S, Parola AH, Fishov I (2003) Phosphatidylethanolamine and phosphatidylglycerol are segregated into different domains in bacterial membrane. A study with pyrene-labelled phospholipids. Mol Microbiol 49:1067–1079
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by M. Kupiec.
Rights and permissions
About this article
Cite this article
Wood, J.M. Perspective: challenges and opportunities for the study of cardiolipin, a key player in bacterial cell structure and function. Curr Genet 64, 795–798 (2018). https://doi.org/10.1007/s00294-018-0811-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-018-0811-2