Abstract
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein, which upon apoptosis induction translocates to the nucleus where it interacts with DNA by virtue of positive charges clustered on the AIF surface. Here we show that the AIF interactome, as determined by mass spectroscopy, contains a large panel of ribonucleoproteins, which apparently bind to AIF through the RNA moiety. However, AIF is devoid of any detectable RNAse activity both in vitro and in vivo. Recombinant AIF can directly bind to DNA as well as to RNA. This binding can be visualized by electron microscopy, revealing that AIF can condense DNA, showing a preferential binding to single-stranded over double-stranded DNA. AIF also binds and aggregates single-stranded and structured RNA in vitro. Single-stranded poly A, poly G and poly C, as well double-stranded A/T and G/C RNA competed with DNA for AIF binding with a similar efficiency, thus corroborating a computer-calculated molecular model in which the binding site within AIF is the same for distinct nucleic acid species, without a clear sequence specificity. Among the preferred electron donors and acceptors of AIF, nicotine adenine dinucleotide phosphate (NADP) was particularly efficient in enhancing the generation of higher-order AIF/DNA and AIF/RNA complexes. Altogether, these data support a model in which a direct interaction of AIF contributes to the compaction of nucleic acids within apoptotic cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- AIF:
-
apoptosis-inducing factor
- NAD:
-
nicotine adenine dinucleotide
- NADP:
-
nicotine adenine dinucleotide phosphate
- TEM:
-
transmission electron microscopy
References
Asselbergs FA, Widmer R . (2003). Anal Biochem 18: 221–229.
Beloin C, Jeusset J, Révet B, Mirambeau G, Le Hegart F, Le Cam E . (2003). J Biol Chem 278: 5333–5342.
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al. (2000). Nucleic Acids Res 28: 235–242.
Cande C, Cecconi F, Dessen P, Kroemer G . (2002). J Cell Sci 115: 4727–4734.
Cande C, Vahsen N, Kouranti I, Schmitt E, Daugas E, Spahr C et al. (2004a). Oncogene 23: 1514–1521.
Cande C, Vahsen N, Metivier D, Tourriere H, Garrido C, Tazi J et al. (2004b). J Cell Sci 117: 4461–4468.
Cheung EC, Melanson-Drapeau L, Cregan SP, Vanderluit JL, Ferguson KL, McIntosh WC et al. (2005). J Neurosci 25: 1324–1334.
Cregan SP, Dawson VL, Slack RS . (2004). Oncogene 23: 2785–2796.
Cregan SP, Fortin A, MacLaurin JG, Callaghan SM, Cecconi F, Park DS et al. (2002). J Cell Biol 158: 507–517.
Crissman HA, Darzynkiewicz Z, Tobey RA, Steinkamp JA . (1985). Science 228: 1321–1324.
Daugas E, Susin SA, Zamzami N, Ferri K, Irinopoulos T, Larochette N et al. (2000). FASEB J 14: 729–739.
Delain E, LeCam E . (1995). The spreading of nucleic acids. In Morel G (ed.), Visualisation of Nucleic Acids. CRC Press: Boca Raton, FL, pp 35–56.
Dubochet J, Ducommun M, Zollinger M, Kellenberger E . (1971). J Ultrastruct Res 35: 147–167.
Gallego M-A, Joseph B, Tamiji S, Mortier L, Kroemer G, Formstecher P et al. (2004). Oncogene 23: 6282–6291.
Garrido C, Kroemer G . (2004). Curr Opin Cell Biol 16: 639–646.
Giordanetto F, Cotesta S, Catana C, Trosset JY, Vulpetti A, Stouten PF et al. (2004). J Chem Inf Comput Sci 44: 882–893.
Green DR, Kroemer G . (2004). Science 305: 626–629.
Gurbuxani S, Schmitt E, Cande C, Parcellier A, Hamman A, Daugas E et al. (2003). Oncogene 22: 6669–6678.
Halicka HD, Bedner E, Darzynkiewicz Z . (2000). Exp Cell Res 260: 248–256.
Hameau L, Jeusset J, Lafosse S, Coulaud D, Delain E, Unge T et al. (2001). J Virol 75: 3301–3313.
Hassan M, Bielawski JP, Hempel JC, Waldman M . (1996). Mol Div 2: 64–74.
Herker E, Jungwirth H, Lehmann KA, Maldener C, Frohlich KU, Wissing S et al. (2004). J Cell Biol 164: 501.
Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CYJ et al. (2001). Nature 410: 549–554.
Kang YH, Yi MJ, Kim MJ, Park MT, Bae S, Kang CM et al. (2004). Cancer Res 64: 8960–8967.
King KL, Jewell CM, Bortner CD, Cidlowski JA . (2000). Cell Death Differ 7: 994–1001.
Klein JA, Longo-Guess CM, Rossmann MP, Seburn KL, Hurd RE, Frankel WN et al. (2002). Nature 419: 367–374.
Kroemer G, Martin SJ . (2005). Nat Med 11: 725–730.
Le Cam E, Coulaud D, Delain E, Petitjean F, Roques BP, Gérard D et al. (1998). Biopolymers 45: 217–229.
Loeffler M, Daugas E, Susin SA, Zamzami N, Métivier D, Nieminen A-L et al. (2001). FASEB J 15: 758–767.
Mate MJ, Ortiz-Lombardia M, Boitel B, Haouzi A, Tello D, Susin SA et al. (2002). Nat Struct Biol 9: 442–446.
Matsumori Y, Hong SM, Aoyama K, Fan Y, Kayama T, Sheldon RA et al. (2005). J Cereb Blood Flow Metab 25: 899–910.
McMartin C, Bohacek RS . (1997). J Comput-Aided Mol Des 11: 333–344.
Miramar MD, Costantini P, Ravagnan L, Saraiva LM, Haouzi D, Brothers G et al. (2001). J Biol Chem 276: 16391–16398.
Otera H, Ohsakaya S, Nagaura ZI, Ishihara N, Mihara K . (2005). EMBO J 24: 1375–1386.
Park MT, Kim MJ, Kang YH, Choi SV, Lee JH, Choi JA et al. (2005). Blood 105: 1724–1733.
Parrish JZ, Xue D . (2003). Mol Cell 11: 987–996.
Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG . (2005). J Biol Chem 280: 6447–6454.
Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N et al. (2001). Nat Cell Biol 3: 839–843.
Rutjes SA, van der Heijden A, Utz PJ, van Venrooij WJ, Pruijn GJ . (1999). J Biol Chem 274: 24799–24807.
Senda T, Yamada T, Sakurai N, Kubota M, Nishizaki T, Masai E et al. (2000). J Mol Biol 304: 397–410.
Susin SA, Daugas E, Ravagnan L, Samejima K, Zamzami N, Loeffler M et al. (2000). J Exp Med 192: 571–579.
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM et al. (1999). Nature 397: 441–446.
Treuner K, Ramsperger U, Knippers R . (1996). J Mol Biol 259: 104–112.
Urbano A, Lakshmanan U, Choo PH, Kwan JC, Ng PY, Guo K et al. (2005). EMBO J 24: 2815–2826.
Vahsen N, Cande C, Briere J-J, Benit P, Joza N, Mastroberardini PG et al. (2004). EMBO J 23: 4679–4689.
Wissing S, Ludovico P, Herker E, Büttner S, Engelhardt SM, Decker T et al. (2004). J Cell Biol 166: 969–974.
Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N et al. (2002). Nat Struct Biol 9: 680–684.
Yuste VJ, Moubarak RS, Delettre C, Bras M, Sancho P, Robert N et al. (2005). Cell Death Differ 280: 35670–35683.
Zhu C, Qiu L, Wang X, Hallin U, Cande C, Kroemer G et al. (2003). J Neurochem 86: 306–317.
Acknowledgements
We thank Nathanael Larochette and Didier Métivier for expert technical assistance. This work was supported by a special grant of the French League against Cancers as well as by grants by the European Union (Trans-Death, Right, Impaled) (to GK), Agence Nationale pour la Recherche sur le SIDA, Association pour la Recherche sur le cancer and the League against Cancer (to ELC). NV received a fellowship from the Association pour la Recherche sur le Cancer.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vahsen, N., Candé, C., Dupaigne, P. et al. Physical interaction of apoptosis-inducing factor with DNA and RNA. Oncogene 25, 1763–1774 (2006). https://doi.org/10.1038/sj.onc.1209206
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209206
Keywords
This article is cited by
-
Exercise-induced sudden cardiac death is caused by mitochondrio-nuclear translocation of AIF
Cell Death & Disease (2021)
-
SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF
Journal of Experimental & Clinical Cancer Research (2019)
-
Multifunctional enzymes in archaea: promiscuity and moonlight
Extremophiles (2013)
-
A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2
Cell Death & Differentiation (2010)
-
An Archaeal NADH Oxidase Causes Damage to Both Proteins and Nucleic Acids under Oxidative Stress
Molecules and Cells (2010)