Prof Stephen Tait - Mitochondria and Cell Death
Introduction
Cell death is a key tumour suppressor mechanism that must be inhibited in order for cancer to develop. Sensitivity to cell death also governs therapeutic efficacy because anti-cancer therapies often act by killing cells. The major form of programmed cell death is apoptosis, a process in which mitochondria play an essential role. Our research focuses upon understanding how mitochondria control cell death and addressing how this is deregulated in cancer. Clinical translation of our findings should lead to improvements of existing therapies and development of new approaches to enable tumour selective killing.
Email
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Biography
Education and qualifications
2001: PhD, University of Sussex, Institute for Animal Health, Pirbright Lab
1996: BSc, Medical Microbiology, University of Edinburgh
Appointments
2012-present: Group Leader, CRUK Scotland Institute / University of Glasgow
2005-2011: Postdoctoral Fellow with Doug Green, St Jude Children's Hospital, Memphis, USA
2003-2005: Postdoctoral Fellow with Jannie Borst, The Netherlands Cancer Institute, Amsterdam
2001-2003: Marie Curie Postdoctoral Fellow, The Netherlands Cancer Institute, Amsterdam
Recent Publications
2024
Borgeaud AC, Ganeva I, Klein C, Stooss A, Ross-Kaschitza D, Wu L, Riley JS, Tait SWG, Lemmin T, Kaufmann T, Kukulski W. Large transient assemblies of Apaf1 constitute the apoptosome in cells. bioRxiv. 2024:2024.2007.2001.600688.
von Mässenhausen A, Schlecht MN, Beer K, Maremonti F, Tonnus W, Belavgeni A, Gavali S, Flade K, Riley JS, Zamora Gonzalez N, Brucker A, Becker JN, Tmava M, Meyer C, Peitzsch M, Hugo C, Gembardt F, Angeli JPF, Bornstein SR, Tait SWG, Linkermann A. Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis. Sci Adv. 2024;10(11):eadk7329.
Vringer E, Heilig R, Riley JS, Black A, Cloix C, Skalka G, Montes-Gómez AE, Aguado A, Lilla S, Walczak H, Gyrd-Hansen M, Murphy DJ, Huang DT, Zanivan S, Tait SW. Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO J. 2024.
Ahmed A, Tait SWG. Tumour immunogenicity goes with the (mitochondrial electron) flow. Mol Oncol. 2024.
Glover HL, Schreiner A, Dewson G, Tait SWG. Mitochondria and cell death. Nat Cell Biol. 2024.
Killarney ST, Tait SWG, Green DR, Wood KC. Sublethal engagement of apoptotic pathways in residual cancer. Trends Cell Biol. 2024(3):225-238.
Montes-Gómez AE, Tait SWG. Getting more bang for their buck: BCL2 inhibitors boost dendritic-cell function to enhance anti-cancer immune surveillance. J Transl Med. 2024(1):317.
2023
Koessinger D, Novo D, Koessinger A, Campos A, Peters J, Dutton L, Paschke P, Zerbst D, Moore M, Mitchell L, Neilson M, Stevenson K, Chalmers A, Tait S, Birch J, Norman J. Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness. Neuro-Oncology Advances. 2023;5:vdad067.
Heilig R, Lee J, Tait SWG. Mitochondrial DNA in cell death and inflammation. Biochem Soc Trans. 2023; 51: 457–472
Killarney ST, Tait SWG, Green DR, Wood KC. Sublethal engagement of apoptotic pathways in residual cancer. Trends Cell Biol. 2023;10.1016/j.tcb.2023.07.005.
Marchi S, Guilbaud E, Tait SWG, Yamazaki T, Galluzzi L. Mitochondrial control of inflammation. Nat Rev Immunol. 2023;23:159-173.
Sneyers F, Kerkhofs M, Speelman-Rooms F, Welkenhuyzen K, La Rovere R, Shemy A, Voet A, Eelen G, Dewerchin M, Tait SWG, Ghesquière B, Bootman MD, Bultynck G. Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing MCL-1-addicted cancer cells. Cell Death Dis. 2023;14(9):600.
Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, Cloix C, Hall-Younger E, Machado Espindola-Netto J, Jurk D, Lagnado AB, Sales Gomez L, Farr JN, Saul D, Reed R, Kelly G, Eppard M, Greaves LC, Dou Z, Pirius N, Szczepanowska K, Porritt RA, Huang H, Huang TY, Mann DA, Masuda CA, Khosla S, Dai H, Kaufmann SH, Zacharioudakis E, Gavathiotis E, LeBrasseur NK, Lei X, Sainz AG, Korolchuk VI, Adams PD, Shadel GS, Tait SWG, Passos JF. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature. 2023.
Vitale I, Pietrocola F, Guilbaud E, Aaronson SA, Abrams JM, Adam D, Agostini M, Agostinis P, Alnemri ES, Altucci L, et al. Apoptotic cell death in disease-Current understanding of the NCCD 2023. Cell Death Differ. 2023;30:1097–1154
Vringer E, Tait SWG. Mitochondria and cell death-associated inflammation. Cell Death Differ. 2023;30:304-312.
2022
Cao K, Riley JS, Heilig R, Montes-Gómez AE, Vringer E, Berthenet K, Cloix C, Elmasry Y, Spiller DG, Ichim G, Campbell KJ, Gilmore AP, Tait SWG. Mitochondrial dynamics regulate genome stability via control of caspase-dependent DNA damage. Developmental Cell. 2022;57:1211-1225
Fanfone D, Wu Z, Mammi J, Berthenet K, Neves D, Weber K, Halaburkova A, Virard F, Bunel F, Jamard C, Hernandez-Vargas H, Tait SWG, Hennino A, Ichim G. Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness. Elife. 2022;11.
Kalkavan H, Chen MJ, Crawford JC, Quarato G, Fitzgerald P, Tait SWG, Goding CR, Green DR. Sublethal cytochrome c release generates drug-tolerant persister cells. Cell. 2022;185:3356-3374.e3322.
Zacharioudakis E, Agianian B, Kumar Mv V, Biris N, Garner TP, Rabinovich-Nikitin I, Ouchida AT, Margulets V, Nordstrøm LU, Riley JS, Dolgalev I, Chen Y, Wittig AJH, Pekson R, Mathew C, Wei P, Tsirigos A, Tait SWG, Kirshenbaum LA, Kitsis RN, Gavathiotis E. Modulating mitofusins to control mitochondrial function and signaling. Nat Commun. 2022;13:3775.
Marchi S, Guilbaud E, Tait SWG, Yamazaki T, Galluzzi L. Mitochondrial control of inflammation. Nature Reviews Immunology. 2022;23:159–173
Rhiner C, Suzanne M, Liu GH, Tait SWG, Torii KU, Ichikawa T, Zhang HT, Liu WC, Sun N. Voicing the story behind the cover. Dev Cell. 2022;57:2679-2682.
Tait SWG. Killing cells using light (activated) sabers. Journal of Cell Biology. 2022;221: e202205018
2021
Bock FJ, Sedov E, Koren E, Koessinger AL, Cloix C, Zerbst D, Athineos D, Anand J, Campbell KJ, Blyth K, Fuchs Y, Tait SWG. Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death. Nat Commun. 2021 Nov 12;12(1):6572.
Campbell KJ, Mason SM, Winder ML, Willemsen RBE, Cloix C, Lawson H, Rooney N, Dhayade S, Sims AH, Blyth K, Tait SWG. Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function. Cell Death Differ. 2021; 28:2589–2600
Johnson SA, Ormsby MJ, Wessel HM, Hulme HE, Bravo-Blas A, McIntosh A, Mason S, Coffelt SB, Tait SWG, Mowat AM, Milling SWF, Blyth K, Wall DM. Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition in a mouse melanoma model. Eur J Immunol. 2021; 51: 3228-3238
Latif AL, Newcombe A, Li S, Gilroy K, Robertson NA, Lei X, Stewart HJS, Cole J, Terradas MT, Rishi L, McGarry L, McKeeve C, Reid C, Clark W, Campos J, Kirschner K, Davis A, Lopez J, Sakamaki JI, Morton JP, et al. BRD4-mediated repression of p53 is a target for combination therapy in AML. Nat Commun. 2021;12:241.
Rabas N, Palmer S, Mitchell L, Ismail S, Gohlke A, Riley JS, Tait SWG, Gammage P, Soares LL, Macpherson IR, Norman JC. PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness. J Cell Biol. 2021;220.
Roca-Portoles A, Tait SWG. Mitochondrial quality control: from molecule to organelle. Cell Mol Life Sci. 2021; 78:3853–3866
2020
Ahmed A, Tait SWG. Targeting Immunogenic Cell Death in Cancer. Mol Oncol. 2020: ed2020.
Koessinger AL, Koessinger D, Stevenson K, Cloix C, Mitchell L, Nixon C, Gomez-Roman N, Chalmers AJ, Norman JC, Tait SWG. Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts. Scientific Reports. 2020;10(1):15361.
Roca-Portoles A, Rodriguez-Blanco G, Sumpton D, Cloix C, Mullin M, Mackay GM, O’Neill K, Lemgruber L, Luo X, Tait SWG. Venetoclax causes metabolic reprogramming independent of BCL-2 inhibition. Cell Death & Disease. 2020;11(8):616.
Stöhr D, Schmid JO, Beigl TB, Mack A, Maichl DS, Cao K, Budai B, Fullstone G, Kontermann RE, Mürdter TE, Tait SWG, Hagenlocher C, Pollak N, Scheurich P, Rehm M. Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids. Cell Death Diff. 2020; 27;3037–3052
Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nature reviews Molecular cell biology. 2020: 21: 85–100
Riley JS, Tait SW. Mitochondrial DNA in inflammation and immunity. EMBO Rep. 2020; 21: e49799
Roca Portoles A, Tait SWG. ER Stress Leaves an Inflammatory TRAIL. Dev Cell. 2020; 52: 678-680
2019
Beaumatin F, O'Prey J, Barthet VJA, Zunino B, Parvy JP, Bachmann AM, O'Prey M, Kania E, Gonzalez PS, Macintosh R, Lao LY, Nixon C, Lopez J, Long JS, Tait SWG, Ryan KM. mTORC1 Activation Requires DRAM-1 by Facilitating Lysosomal Amino Acid Efflux. Molecular cell. 2019; 76: 163–17
Cao K, Tait SWG. Parkin inhibits necroptosis to prevent cancer. Nature cell biology. 2019;21:915-916.
Lopez J, Tait SWG. Application of Mito-Priming to Generate BCL-2 Addicted Cells. Methods in molecular biology (Clifton, NJ) 2019;1877:45-60.
Orozco SL, Daniels BP, Yatim N, Messmer MN, Quarato G, Chen-Harris H, Cullen SP, Snyder AG, Ralli-Jain P, Frase S, Tait SWG, Green DR, Albert ML, Oberst A. RIPK3 Activation Leads to Cytokine Synthesis that Continues after Loss of Cell Membrane Integrity. Cell reports. 2019; 28: 2275-2287
Riley JS, Tait SW. Mitochondria and pathogen immunity: from killer to firestarter. The EMBO journal. 2019;38: e102325
Vringer E, Tait SWG. Mitochondria and Inflammation: Cell Death Heats Up. Frontiers in cell and developmental biology. 2019;7:100.
2018
Riley JS, Quarato G, Cloix C, Lopez J, O'Prey J, Pearson M, Chapman J, Sesaki H, Carlin LM, Passos JF, Wheeler AP, Oberst A, Ryan KM, Tait SW. Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis. EMBO J. 2018; 37: e99238
Bock FJ, Tait SWG. p53 REEPs to sow ER-mitochondrial contacts. Cell Res. 2018; 28: 877–878
Campbell KJ, Tait SWG. Targeting BCL-2 regulated apoptosis in cancer. Open Biol. 2018; 8:
Giampazolias E, Tait SWG. Caspase-independent cell death: An anti-cancer double whammy. Cell cycle. 2018; 17: 269-270.
2017
Correia-Melo C, Ichim G, Tait SW, Passos JF. Depletion of mitochondria in mammalian cells through enforced mitophagy. Nat Protoc 2017; 12: 183-94
Daniels BP, Snyder AG, Olsen TM, Orozco S, Oguin TH, 3rd, Tait SW, Martinez J, Gale M, Jr., Loo YM, Oberst A. RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation. Cell 2017; 169: 301-13.e11
Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C, Cao K, Roca A, Lopez J, Ichim G, Proics E, Rubio-Patino C, Fort L, Yatim N, Woodham E, Orozco S, Taraborrelli L, Peltzer N, Lecis D, Machesky L, Walczak H et al. Mitochondrial permeabilization engages NF-kappaB-dependent anti-tumour activity under caspase deficiency. Nat Cell Biol 2017; 19: 1116-29
Gutierrez KD, Davis MA, Daniels BP, Olsen TM, Ralli-Jain P, Tait SW, Gale M, Jr., Oberst A. MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1beta Independently of Gasdermin-D. J Immunol 2017; 195: 2156-64
Villa E, Proics E, Rubio-Patino C, Obba S, Zunino B, Bossowski JP, Rozier RM, Chiche J, Mondragon L, Riley JS, Marchetti S, Verhoeyen E, Tait SWG, Ricci JE. Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells. Cell Rep 2017; 20: 2846-59
Weigert M, Binks A, Dowson S, Leung EYL, Athineos D, Yu X, Mullin M, Walton JB, Orange C, Ennis D, Blyth K, Tait SWG, McNeish IA. RIPK3 promotes adenovirus type 5 activity. Cell Death and Disease 2017; 8: 3206
Woodham EF, Paul NR, Tyrrell B, Spence HJ, Swaminathan K, Scribner MR, Giampazolias E, Hedley A, Clark W, Kage F, Marston DJ, Hahn KM, Tait SW, Larue L, Brakebusch CH, Insall RH, Machesky LM. Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Curr Biol 2017; 27: 624-37
Giampazolias E, Tait SWG. Caspase-independent cell death: an anti-cancer double-whammy. Cell Cycle 2017; 17: 269-270
Ichim G, Tait SWG. Cancer therapy-induced PAFR ligand expression: any role for caspase activity? Nat Rev Cancer 2017; 17: 253
Simon HU, Friis R, Tait SW, Ryan KM. Retrograde signaling from autophagy modulates stress responses. Sci Signal 2017; 10: eaag2791.
2016
Correia-Melo C, Ichim G, Tait SW, Passos JF. Depletion of mitochondria in mammalian cells through enforced mitophagy. Nat Protoc 2017; 12: 183-94. doi: 10.1038/nprot.2016.159. Epub 22 Dec 2016Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SW, Czapiewski R, Greaves L, Nelson G, Bohlooly-Y M, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J. 2016; 35: 724-42
Lopez J, Bessou M, Riley JS, Giampazolias E, Todt F, Rochegue T, Oberst A, Green DR, Edlich F, Ichim G, Tait SWG. Mito-priming as a method to engineer Bcl-2 addiction. Nat Commun 2016; 7: 10538
Pecot J, Maillet L, Le Pen J, Vuillier C, Trecesson SC, Fetiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SW, Gautier F, Juin PP. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Cell Rep. 2016; 17: 3347-3358
Giampazolias E, Tait SWG. Mitochondria and the hallmarks of cancer. FEBS J. 2016; 283: 803-14
Ichim G, Tait SWG. A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer. 2016; 16: 539-48
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12: 1-222
Oberst A, Ichim G, Tait SWG. Mitochondrial Permeabilization: From Lethality to Vitality. In: Cell Death in Biology and Diseases pp 213-26, 2016 (Ed Hockenbery DM)
Riley JS, Tait SWG. Mechanisms of mitophagy: putting the powerhouse into the doghouse. Biol Chem. 2016; 397: 617-35
