Wellcome Trust Centre For Mitochondrial Research

Professor Robert Lightowlers

Personal Biography

bob-resizeI was awarded my B.Sc (Hons) in Biological Sciences from the University of East Anglia in 1983. I moved to the Australian National University in Canberra to study for a Ph.D in Microbial Genetics (and learn to surf) under the supervision of Professors Frank Gibson and Graeme Cox, graduating in 1988. Following a postdoctoral position with Professor Rod Capaldi at the Institute of Molecular Biology in Eugene Oregon USA, where I gained my lifelong interest in mitochondria and mitochondrial disease, I successfully applied for a Lister Institute Fellowship in 1990. This allowed me to return to the UK, where I established my laboratory at Newcastle University to study the molecular mechanisms of mitochondrial gene expression and disease. I have been employed by Newcastle University since that date, being awarded a Personal Chair in 2000. From my close interaction with Professor Turnbull, the Mitochondrial Research Group was initiated. This has expanded enormously and led to formation of the Wellcome Trust Centre for Mitochondrial Research in 2012. I was appointed Director of the Institute for Cell and Molecular Biosciences in 2012.

Research Biography

My postgraduate studies were on the function of the ATP synthase in eubacteria. It was therefore not such a large step to studying oxidative phosphorylation in man, which I started in the US in 1988. Mutations of the mitochondrial genome (mtDNA) were shown to cause disease and my main research topic since this time has been into determining the molecular mechanisms that underlie expression of this genome in man and searching for a cure for these disorders. This has proved to be particularly complicated, as it is not yet possible to transfect mammalian mitochondria in intact cells and there is no faithful reconstituted system for studying mitochondrial protein synthesis. The multi-copy nature of mtDNA has also led to a fascination with mitochondrial genetics and transmission. Studying pathogenic mutations, both in the nucleus and in mtDNA, that result in defects of mitochondrial gene expression, has helped us understand far more about these complex mechanisms and through these insights we hope to be able to offer treatments that are currently not available for the majority of patients with mitochondrial disease.

Awards, honours and professional service

1998 Ph.D John Curtin School of Medical Research, Australian National University

1996-present Member of the Lister Institute of Preventive Medicine

1997 Henry Wellcome Commemorative Award for Innovative Research

1998-present Member, Biochemical Society

1997 Member, Advisory panel to the French Government on use of nucleoside analogues in AIDS research

1998 Erskine Prize, University of Canterbury, Christchurch New Zealand

2000 Professor of Molecular Neuroscience, Newcastle University

2001-2012 Scientific advisory panel for Ataxia UK

2005-2009 MRC College of Experts

2008-2011  BBSRC Pool of Experts

2011-present Finnish Academy of Science Scientific Review Board 2011-present

2012 Director, Institute for Cell and Molecular Biosciences, Newcastle University

2012 Royal Swedish Academy of Science Evaluation for Goran Gustafsson Prize

2013 -Research Council of Norway Scientific Review Board 2013

 

Recent Key Publications

 

Mutations causing mitochondrial disease: What is new and what challenges remain? Lightowlers RN, Taylor RW, Turnbull DM (2015) Science. 349: 1494-9.

Oláhová M, Hardy SA, Hall J, Yarham JW, Haack TB, Wilson WC, Alston, CL, He L, Aznauryan E, Brown RM, Brown GK, Morris AAM, Mundy H, Broomfield A, Barbosa IA, Simpson MA, Deshpande C, Moeslinger D, Koch J, Stettner GM, Bonnen PE, Prokisch H, Lightowlers RN, McFarland R, Chrzanowska-Lightowlers ZMA, Taylor RW (2015) LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French Canadian population. Brain, 138(12) 3503-19.

Rai PK, Russell OM, Lightowlers RN, Turnbull DM. Potential compounds for the treatment of mitochondrial disease. Br Med Bull. 2015 116(1):5-18.

Wilson, WC, Hornig-Do H-T, Bruni F, Chang JH, Jourdain AA, Martinou J-C, Falkenberg M, Spåhr H, Larsson N-G, Lewis RJ, Hewitt L, Baslé A, Cross HE, Tong L, Lebel RR, Crosby AH, Chrzanowska-Lightowlers ZMA*, Lightowlers RN*. A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression. Hum. Mol. Genet. 2014;23:6345-6355.

Hornig-Do H-T, Montanari A, Rozanska A, Tuppen HA, Almalki AA, Abg-Kamaludin DP, Frontali L, Francisci S, Lightowlers RN*, Chrzanowska-Lightowlers ZMA*. Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt-tRNA mutations. EMBO Mol. Med.  2014;6:183-193.

Jourdain AA, Koppen M, Wydro M, Rodley CD, Lightowlers RN, Chrzanowska-Lightowlers ZMA, Martinou JC. GRSF1 Regulates RNA Processing in Mitochondrial RNA Granules. Cell Metab. 2013;17:399-410.

Temperley R, Richter R, Dennerlein S, Lightowlers RN*, Chrzanowska-Lightowlers ZMA*. Hungry codons promote frameshifting in human mitochondrial ribosomes. Science 2010;327:301

Richter R, Rorbach J, Pajak A, Smith PM, Wessels H J, Huynen MA, Smeitink J A, Lightowlers RN*, Chrzanowska-Lightowlers ZMA*. A functional peptidyl tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010;29:1116-1125.

Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K, Sharifi R, Harlalka G, Dick K, Reed J, Al-Memar A, Chrzanowksa-Lightowlers ZMA, Cross H, Lightowlers RN. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am. J. Hum. Genet. 2010;87:655-660.

Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010 May 6;465(7294):82-5

 

Publications

Russell OM; Lightowlers RN; Turnbull DM, 2016. Applying the Airbrakes: Treating Mitochondrial Disease with Hypoxia.  Mol Cell 62(1):5-6

Oláhová M; Haack TB; Alston CL; Houghton JA; He L; Morris AA; Brown GK; McFarland R; Chrzanowska-Lightowlers ZM; Lightowlers RN; Prokisch H; Taylor RW, 2015. A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency.  Eur J Hum Genet 23(7):935-9

Elson JL; Smith PM; Greaves LC; Lightowlers RN; Chrzanowska-Lightowlers ZM; Taylor RW; Vila-Sanjurjo A, 2015. The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease.  Mitochondrion 25:17-27

Chrzanowska-Lightowlers ZM; Lightowlers RN, 2015. Response to "Ribosome Rescue and Translation Termination at Non-standard Stop Codons by ICT1 in Mammalian Mitochondria".  PLoS Genet 11(6):e1005227

Lightowlers RN; Taylor RW; Turnbull DM, 2015. Mutations causing mitochondrial disease: What is new and what challenges remain?  Science 349(6255):1494-9

Oláhová M; Hardy SA; Hall J; Yarham JW; Haack TB; Wilson WC; Alston CL; He L; Aznauryan E; Brown RM; Brown GK; Morris AA; Mundy H; Broomfield A; Barbosa IA; Simpson MA; Deshpande C; Moeslinger D; Koch J; Stettner GM; Bonnen PE; Prokisch H; Lightowlers RN; McFarland R; Chrzanowska-Lightowlers ZM; Taylor RW, 2015. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.  Brain 138(Pt 12):3503-19

Rai PK; Russell OM; Lightowlers RN; Turnbull DM, 2015. Potential compounds for the treatment of mitochondrial disease.  Br Med Bull 116:5-18

Almalki A; Alston CL; Parker A; Simonic I; Mehta SG; He L; Reza M; Oliveira JM; Lightowlers RN; McFarland R; Taylor RW; Chrzanowska-Lightowlers ZM, 2014. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.  Biochim Biophys Acta 1842(1):56-64

Meagher M; Lightowlers RN, 2014. The role of TDP1 and APTX in mitochondrial DNA repair.  Biochimie 100:121-4

Smith PM; Elson JL; Greaves LC; Wortmann SB; Rodenburg RJ; Lightowlers RN; Chrzanowska-Lightowlers ZM; Taylor RW; Vila-Sanjurjo A, 2014. The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential.  Hum Mol Genet 23(4):949-67

Hornig-Do HT; Montanari A; Rozanska A; Tuppen HA; Almalki AA; Abg-Kamaludin DP; Frontali L; Francisci S; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2014. Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt-tRNA mutations.  EMBO Mol Med 6(2):183-93

Lightowlers RN; Chrzanowska-Lightowlers ZM, 2014. Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?  EMBO Mol Med 6(6):705-7

Wesolowska MT; Richter-Dennerlein R; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2014. Overcoming stalled translation in human mitochondria.  Front Microbiol 5:374

Wilson WC; Hornig-Do HT; Bruni F; Chang JH; Jourdain AA; Martinou JC; Falkenberg M; Spåhr H; Larsson NG; Lewis RJ; Hewitt L; Baslé A; Cross HE; Tong L; Lebel RR; Crosby AH; Chrzanowska-Lightowlers ZM; Lightowlers RN, 2014. A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression.  Hum Mol Genet 23(23):6345-55

Lightowlers RN; Rozanska A; Chrzanowska-Lightowlers ZM, 2014. Mitochondrial protein synthesis: figuring the fundamentals, complexities and complications, of mammalian mitochondrial translation.  FEBS Lett 588(15):2496-503

Jourdain AA; Koppen M; Wydro M; Rodley CD; Lightowlers RN; Chrzanowska-Lightowlers ZM; Martinou JC, 2013. GRSF1 regulates RNA processing in mitochondrial RNA granules.  Cell Metab 17(3):399-410

Lightowlers RN; Chrzanowska-Lightowlers ZM, 2013. Human pentatricopeptide proteins: only a few and what do they do?  RNA Biol 10(9):1433-8

Bruni F; Gramegna P; Oliveira JM; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2013. REXO2 is an oligoribonuclease active in human mitochondria.  PLoS One 8(5):e64670

Wessels HJ; Vogel RO; Lightowlers RN; Spelbrink JN; Rodenburg RJ; van den Heuvel LP; van Gool AJ; Gloerich J; Smeitink JA; Nijtmans LG, 2013. Analysis of 953 human proteins from a mitochondrial HEK293 fraction by complexome profiling.  PLoS One 8(7):e68340

Challen C; Anderson JJ; Chrzanowska-Lightowlers ZM; Lightowlers RN; Lunec J, 2012. Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA.  Int J Oncol 40(3):851-9

Wanschers BF; Szklarczyk R; Pajak A; van den Brand MA; Gloerich J; Rodenburg RJ; Lightowlers RN; Nijtmans LG; Huynen MA, 2012. C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation.  Nucleic Acids Res 40(9):4040-51

Lightowlers RN; Chrzanowska-Lightowlers ZM, 2012. Exploring our origins--the importance of OriL in mtDNA maintenance and replication.  EMBO Rep 13(12):1038-9

Bruni F; Gramegna P; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2012. The mystery of mitochondrial RNases.  Biochem Soc Trans 40(4):865-9

Chrzanowska-Lightowlers ZM; Horvath R; Lightowlers RN, 2011. 175th ENMC International Workshop: Mitochondrial protein synthesis in health and disease, 25-27th June 2010, Naarden, The Netherlands.  Neuromuscul Disord 21(2):142-7

Boesch P; Weber-Lotfi F; Ibrahim N; Tarasenko V; Cosset A; Paulus F; Lightowlers RN; Dietrich A, 2011. DNA repair in organelles: Pathways, organization, regulation, relevance in disease and aging.  Biochim Biophys Acta 1813(1):186-200

Smith PM; Lightowlers RN, 2011. Altering the balance between healthy and mutated mitochondrial DNA.  J Inherit Metab Dis 34(2):309-13

Kolanczyk M; Pech M; Zemojtel T; Yamamoto H; Mikula I; Calvaruso MA; van den Brand M; Richter R; Fischer B; Ritz A; Kossler N; Thurisch B; Spoerle R; Smeitink J; Kornak U; Chan D; Vingron M; Martasek P; Lightowlers RN; Nijtmans L; Schuelke M; Nierhaus KH; Mundlos S, 2011. NOA1 is an essential GTPase required for mitochondrial protein synthesis.  Mol Biol Cell 22(1):1-11

Kemp JP; Smith PM; Pyle A; Neeve VC; Tuppen HA; Schara U; Talim B; Topaloglu H; Holinski-Feder E; Abicht A; Czermin B; Lochmüller H; McFarland R; Chinnery PF; Chrzanowska-Lightowlers ZM; Lightowlers RN; Taylor RW; Horvath R, 2011. Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.  Brain 134(Pt 1):183-95

Ibrahim N; Handa H; Cosset A; Koulintchenko M; Konstantinov Y; Lightowlers RN; Dietrich A; Weber-Lotfi F, 2011. DNA delivery to mitochondria: sequence specificity and energy enhancement.  Pharm Res 28(11):2871-82

Chrzanowska-Lightowlers ZM; Pajak A; Lightowlers RN, 2011. Termination of protein synthesis in mammalian mitochondria.  J Biol Chem 286(40):34479-85

Mileshina D; Ibrahim N; Boesch P; Lightowlers RN; Dietrich A; Weber-Lotfi F, 2011. Mitochondrial transfection for studying organellar DNA repair, genome maintenance and aging.  Mech Ageing Dev 132(8-9):412-23

Lightowlers RN, 2011. Mitochondrial transformation: time for concerted action.  EMBO Rep 12(6):480-1

Bruni F; Lightowlers RN, 2011. Designing an organellar postal service: delivery of macromolecules to mitochondria in intact cells.  Mol Ther 19(8):1404-5

Richter R; Rorbach J; Pajak A; Smith PM; Wessels HJ; Huynen MA; Smeitink JA; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome.  EMBO J 29(6):1116-25

Trevelyan AJ; Kirby DM; Smulders-Srinivasan TK; Nooteboom M; Acin-Perez R; Enriquez JA; Whittington MA; Lightowlers RN; Turnbull DM, 2010. Mitochondrial DNA mutations affect calcium handling in differentiated neurons.  Brain 133(Pt 3):787-96

Abramov AY; Smulders-Srinivasan TK; Kirby DM; Acin-Perez R; Enriquez JA; Lightowlers RN; Duchen MR; Turnbull DM, 2010. Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations.  Brain 133(Pt 3):797-807

Nooteboom M; Johnson R; Taylor RW; Wright NA; Lightowlers RN; Kirkwood TB; Mathers JC; Turnbull DM; Greaves LC, 2010. Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts.  Aging Cell 9(1):96-9

Boesch P; Ibrahim N; Dietrich A; Lightowlers RN, 2010. Membrane association of mitochondrial DNA facilitates base excision repair in mammalian mitochondria.  Nucleic Acids Res 38(5):1478-88

Temperley R; Richter R; Dennerlein S; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. Hungry codons promote frameshifting in human mitochondrial ribosomes.  Science 327(5963):301

Wydro M; Bobrowicz A; Temperley RJ; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes mitochondrial translation inhibition.  Nucleic Acids Res 38(11):3732-42

Dennerlein S; Rozanska A; Wydro M; Chrzanowska-Lightowlers ZM; Lightowlers RN, 2010. Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit.  Biochem J 430(3):551-8

Oliveira JM; Lightowlers RN, 2010. Could successful (mitochondrial) networking help prevent Huntington's disease?  EMBO Mol Med 2(12):487-9

Temperley RJ; Wydro M; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. Human mitochondrial mRNAs--like members of all families, similar but different.  Biochim Biophys Acta 1797(6-7):1081-5

Crosby AH; Patel H; Chioza BA; Proukakis C; Gurtz K; Patton MA; Sharifi R; Harlalka G; Simpson MA; Dick K; Reed JA; Al-Memar A; Chrzanowska-Lightowlers ZM; Cross HE; Lightowlers RN, 2010. Defective mitochondrial mRNA maturation is associated with spastic ataxia.  Am J Hum Genet 87(5):655-60

Richter R; Pajak A; Dennerlein S; Rozanska A; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. Translation termination in human mitochondrial ribosomes.  Biochem Soc Trans 38(6):1523-6

Wang G; Chen HW; Oktay Y; Zhang J; Allen EL; Smith GM; Fan KC; Hong JS; French SW; McCaffery JM; Lightowlers RN; Morse HC 3rd; Koehler CM; Teitell MA, 2010. PNPASE regulates RNA import into mitochondria.  Cell 142(3):456-67

Craven L; Tuppen HA; Greggains GD; Harbottle SJ; Murphy JL; Cree LM; Murdoch AP; Chinnery PF; Taylor RW; Lightowlers RN; Herbert M; Turnbull DM, 2010. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.  Nature 465(7294):82-5

Lightowlers RN; Chrzanowska-Lightowlers ZM, 2010. Terminating human mitochondrial protein synthesis: a shift in our thinking.  RNA Biol 7(3):282-6

Weber-Lotfi F; Ibrahim N; Boesch P; Cosset A; Konstantinov Y; Lightowlers RN; Dietrich A, 2009. Developing a genetic approach to investigate the mechanism of mitochondrial competence for DNA import.  Biochim Biophys Acta 1787(5):320-7

McDonald BM; Wydro MM; Lightowlers RN; Lakey JH, 2009. Probing the orientation of yeast VDAC1 in vivo.  FEBS Lett 583(4):739-42

Kirby DM; Rennie KJ; Smulders-Srinivasan TK; Acin-Perez R; Whittington M; Enriquez JA; Trevelyan AJ; Turnbull DM; Lightowlers RN, 2009. Transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations are compromised in neuronal differentiation.  Cell Prolif 42(4):413-24

Horvath R; Kemp JP; Tuppen HA; Hudson G; Oldfors A; Marie SK; Moslemi AR; Servidei S; Holme E; Shanske S; Kollberg G; Jayakar P; Pyle A; Marks HM; Holinski-Feder E; Scavina M; Walter MC; Coku J; Günther-Scholz A; Smith PM; McFarland R; Chrzanowska-Lightowlers ZM; Lightowlers RN; Hirano M; Lochmüller H; Taylor RW; Chinnery PF; Tulinius M; DiMauro S, 2009. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.  Brain 132(Pt 11):3165-74

Rorbach J; Yusoff AA; Tuppen H; Abg-Kamaludin DP; Chrzanowska-Lightowlers ZM; Taylor RW; Turnbull DM; McFarland R; Lightowlers RN, 2008. Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation.  Nucleic Acids Res 36(9):3065-74

Reeve AK; Krishnan KJ; Elson JL; Morris CM; Bender A; Lightowlers RN; Turnbull DM, 2008. Nature of mitochondrial DNA deletions in substantia nigra neurons.  Am J Hum Genet 82(1):228-35

Bobrowicz AJ; Lightowlers RN; Chrzanowska-Lightowlers Z, 2008. Polyadenylation and degradation of mRNA in mammalian mitochondria: a missing link?  Biochem Soc Trans 36(Pt 3):517-9

Krishnan KJ; Reeve AK; Samuels DC; Chinnery PF; Blackwood JK; Taylor RW; Wanrooij S; Spelbrink JN; Lightowlers RN; Turnbull DM, 2008. What causes mitochondrial DNA deletions in human cells?  Nat Genet 40(3):275-9

Kyriakouli DS; Boesch P; Taylor RW; Lightowlers RN, 2008. Progress and prospects: gene therapy for mitochondrial DNA disease.  Gene Ther 15(14):1017-23

Lightowlers RN; Chrzanowska-Lightowlers ZM, 2008. PPR (pentatricopeptide repeat) proteins in mammals: important aids to mitochondrial gene expression.  Biochem J 416(1):e5-6

Rorbach J; Richter R; Wessels HJ; Wydro M; Pekalski M; Farhoud M; Kühl I; Gaisne M; Bonnefoy N; Smeitink JA; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2008. The human mitochondrial ribosome recycling factor is essential for cell viability.  Nucleic Acids Res 36(18):5787-99

Leontiou C; Watters GP; Gilroy KL; Heslop P; Cowell IG; Craig K; Lightowlers RN; Lakey JH; Austin CA, 2007. Differential selection of acridine resistance mutations in human DNA topoisomerase IIbeta is dependent on the acridine structure.  Mol Pharmacol 71(4):1006-14

Rorbach J; Soleimanpour-Lichaei R; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2007. How do mammalian mitochondria synthesize proteins?  Biochem Soc Trans 35(Pt 5):1290-1

Betts J; Jaros E; Perry RH; Schaefer AM; Taylor RW; Abdel-All Z; Lightowlers RN; Turnbull DM, 2006. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement.  Neuropathol Appl Neurobiol 32(4):359-73

Brown DT; Herbert M; Lamb VK; Chinnery PF; Taylor RW; Lightowlers RN; Craven L; Cree L; Gardner JL; Turnbull DM, 2006. Transmission of mitochondrial DNA disorders: possibilities for the future.  Lancet 368(9529):87-9

Koulintchenko M; Temperley RJ; Mason PA; Dietrich A; Lightowlers RN, 2006. Natural competence of mammalian mitochondria allows the molecular investigation of mitochondrial gene expression.  Hum Mol Genet 15(1):143-54

Pye D; Kyriakouli DS; Taylor GA; Johnson R; Elstner M; Meunier B; Chrzanowska-Lightowlers ZM; Taylor RW; Turnbull DM; Lightowlers RN, 2006. Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants.  Nucleic Acids Res 34(13):e95

Maniura-Weber K; Helm M; Engemann K; Eckertz S; Möllers M; Schauen M; Hayrapetyan A; von Kleist-Retzow JC; Lightowlers RN; Bindoff LA; Wiesner RJ, 2006. Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNALeu(UUR)) gene.  Nucleic Acids Res 34(22):6404-15

Keresztessy Z; Csosz E; Hársfalvi J; Csomós K; Gray J; Lightowlers RN; Lakey JH; Balajthy Z; Fésüs L, 2006. Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2.  Protein Sci 15(11):2466-80

Elson JL; Lightowlers RN, 2006. Mitochondrial DNA clonality in the dock: can surveillance swing the case?  Trends Genet 22(11):603-7

Seal R; Temperley R; Wilusz J; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2005. Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability.  Nucleic Acids Res 33(1):376-87

Stocksley MA; Awad SS; Young C; Lightowlers RN; Brenner HR; Slater CR, 2005. Accumulation of Nav1 mRNAs at differentiating postsynaptic sites in rat soleus muscles.  Mol Cell Neurosci 28(4):694-702

Pye D; Watt DJ; Walker C; Lightowlers RN; Turnbull DM, 2004. Identification of the RAG-1 as a suitable mouse model for mitochondrial DNA disease.  Neuromuscul Disord 14(5):329-36

Betts J; Lightowlers RN; Turnbull DM, 2004. Neuropathological aspects of mitochondrial DNA disease.  Neurochem Res 29(3):505-11

Blakely EL; He L; Taylor RW; Chinnery PF; Lightowlers RN; Schaefer AM; Turnbull DM, 2004. Mitochondrial DNA deletion in "identical" twin brothers.  J Med Genet 41(2):e19

Chrzanowska-Lightowlers ZM; Temperley RJ; Smith PM; Seneca SH; Lightowlers RN, 2004. Functional polypeptides can be synthesized from human mitochondrial transcripts lacking termination codons.  Biochem J 377(Pt 3):725-31

Gagliardi D; Stepien PP; Temperley RJ; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2004. Messenger RNA stability in mitochondria: different means to an end.  Trends Genet 20(6):260-7

Smith PM; Ross GF; Taylor RW; Turnbull DM; Lightowlers RN, 2004. Strategies for treating disorders of the mitochondrial genome.  Biochim Biophys Acta 1659(2-3):232-9

McFarland R; Taylor RW; Elson JL; Lightowlers RN; Turnbull DM; Howell N, 2004. Proving pathogenicity: when evolution is not enough.  Am J Med Genet A 131(1):107-8; author reply 109-10

Bidooki S; Jackson MJ; Johnson MA; Chrzanowska-Lightowlers ZM; Taylor RW; Venables G; Lightowlers RN; Turnbull DM; Bindoff LA, 2004. Sporadic mitochondrial myopathy due to a new mutation in the mitochondrial tRNASer(UCN) gene.  Neuromuscul Disord 14(7):417-20

Kolesnikova OA; Entelis NS; Jacquin-Becker C; Goltzene F; Chrzanowska-Lightowlers ZM; Lightowlers RN; Martin RP; Tarassov I, 2004. Nuclear DNA-encoded tRNAs targeted into mitochondria can rescue a mitochondrial DNA mutation associated with the MERRF syndrome in cultured human cells.  Hum Mol Genet 13(20):2519-34

Taylor RW; Giordano C; Davidson MM; d'Amati G; Bain H; Hayes CM; Leonard H; Barron MJ; Casali C; Santorelli FM; Hirano M; Lightowlers RN; DiMauro S; Turnbull DM, 2003. A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy.  J Am Coll Cardiol 41(10):1786-96

Mason PA; Matheson EC; Hall AG; Lightowlers RN, 2003. Mismatch repair activity in mammalian mitochondria.  Nucleic Acids Res 31(3):1052-8

James AM; Blaikie FH; Smith RA; Lightowlers RN; Smith PM; Murphy MP, 2003. Specific targeting of a DNA-alkylating reagent to mitochondria. Synthesis and characterization of [4-((11aS)-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-on-8-oxy)butyl]-triphenylphosphonium iodide.  Eur J Biochem 270(13):2827-36

Wardell TM; Ferguson E; Chinnery PF; Borthwick GM; Taylor RW; Jackson G; Craft A; Lightowlers RN; Howell N; Turnbull DM, 2003. Changes in the human mitochondrial genome after treatment of malignant disease.  Mutat Res 525(1-2):19-27

McGregor A; Smith PM; Ross GF; Taylor RW; Turnbull DM; Lightowlers RN, 2003. Bridging PNAs can bind preferentially to a deleted mitochondrial DNA template but replication by mitochondrial DNA polymerase gamma in vitro is not impaired.  Biochim Biophys Acta 1629(1-3):73-83

Temperley RJ; Seneca SH; Tonska K; Bartnik E; Bindoff LA; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2003. Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria.  Hum Mol Genet 12(18):2341-8

Ross GF; Smith PM; McGregor A; Turnbull DM; Lightowlers RN, 2003. Synthesis of trifunctional PNA-benzophenone derivatives for mitochondrial targeting, selective DNA binding, and photo-cross-linking.  Bioconjug Chem 14(5):962-6

Mason PA; Lightowlers RN, 2003. Why do mammalian mitochondria possess a mismatch repair activity?  FEBS Lett 554(1-2):6-9

McFarland R; Clark KM; Morris AA; Taylor RW; Macphail S; Lightowlers RN; Turnbull DM, 2002. Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation.  Nat Genet 30(2):145-6

Turnbull DM; Lightowlers RN, 2002. A roundabout route to gene therapy.  Nat Genet 30(4):345-6

Herrnstadt C; Preston G; Andrews R; Chinnery P; Lightowlers RN; Turnbull DM; Kubacka I; Howell N, 2002. A high frequency of mtDNA polymorphisms in HeLa cell sublines.  Mutat Res 501(1-2):19-28

Muratovska A; Lightowlers RN; Taylor RW; Turnbull DM; Smith RA; Wilce JA; Martin SW; Murphy MP, 2001. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: implications for mitochondrial DNA replication, expression and disease.  Nucleic Acids Res 29(9):1852-63

Taylor RW; Wardell TM; Smith PM; Muratovska A; Murphy MP; Turnbull DM; Lightowlers RN, 2001. An antigenomic strategy for treating heteroplasmic mtDNA disorders.  Adv Drug Deliv Rev 49(1-2):121-5

Chrzanowska-Lightowlers Z; Lightowlers RN, 2001. Fending off decay: a combinatorial approach in intact cells for identifying mRNA stability elements.  RNA 7(3):435-44

Selwood SP; McGregor A; Lightowlers RN; Chrzanowska-Lightowlers ZM, 2001. Inhibition of mitochondrial protein synthesis promotes autonomous regulation of mtDNA expression and generation of a new mitochondrial RNA species.  FEBS Lett 494(3):186-91

Muratovska A; Lightowlers RN; Taylor RW; Wilce JA; Murphy MP, 2001. Targeting large molecules to mitochondria.  Adv Drug Deliv Rev 49(1-2):189-98

Elson JL; Andrews RM; Chinnery PF; Lightowlers RN; Turnbull DM; Howell N, 2001. Analysis of European mtDNAs for recombination.  Am J Hum Genet 68(1):145-153

Taylor RW; Wardell TM; Connolly BA; Turnbull DM; Lightowlers RN, 2001. Linked oligodeoxynucleotides show binding cooperativity and can selectively impair replication of deleted mitochondrial DNA templates.  Nucleic Acids Res 29(16):3404-12

Lightowlers RN; Lill R, 2001. High-level mitochondriology at high altitude. Workshop on mitochondrial (dys-)function.  EMBO Rep 2(12):1074-7

Turnbull DM; Lightowlers RN; Taylor RW, 2001. Current perspectives in the treatment of mitochondrial DNA diseases.  Funct Neurol 16(4 Suppl):89-96

Awad SS; Lightowlers RN; Young C; Chrzanowska-Lightowlers ZM; Lomo T; Slater CR, 2001. Sodium channel mRNAs at the neuromuscular junction: distinct patterns of accumulation and effects of muscle activity.  J Neurosci 21(21):8456-63

Turnbull DM; Lightowlers RN, 2001. Might mammalian mitochondria merge?  Nat Med 7(8):895-6

McGregor A; Temperley R; Chrzanowska-Lightowlers ZM; Lightowlers RN, 2001. Absence of expression from RNA internalised into electroporated mammalian mitochondria.  Mol Genet Genomics 265(4):721-9

Chinnery PF; Taylor RW; Diekert K; Lill R; Turnbull DM; Lightowlers RN, 2000. Peptide nucleic acid and delivery to human mitochondria  Gene Ther 7(9):813

Selwood SP; Chrzanowska-Lightowlers ZM; Lightowlers RN, 2000. Does the mitochondrial transcription-termination complex play an essential role in controlling differential transcription of the mitochondrial DNA?  Biochem Soc Trans 28(2):154-9

Morris AA; Lightowlers RN, 2000. Can paternal mtDNA be inherited?  Lancet 355(9212):1290-1

Nagy E; Henics T; Eckert M; Miseta A; Lightowlers RN; Kellermayer M, 2000. Identification of the NAD(+)-binding fold of glyceraldehyde-3-phosphate dehydrogenase as a novel RNA-binding domain.  Biochem Biophys Res Commun 275(2):253-60

Taylor RW; Chinnery PF; Turnbull DM; Lightowlers RN, 2000. In-vitro genetic modification of mitochondrial function.  Hum Reprod 15 Suppl 2:79-85

Morris AA; Lightowlers RN, 2000. Mitochondrial DNA recombination.  Lancet 356(9233):941

Chinnery PF; Thorburn DR; Samuels DC; White SL; Dahl HM; Turnbull DM; Lightowlers RN; Howell N, 2000. The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both?  Trends Genet 16(11):500-5

Taylor RW; Wardell TM; Lightowlers RN; Turnbull DM, 2000. Molecular basis for treatment of mitochondrial myopathies.  Neurol Sci 21(5 Suppl):S909-12

Lightowlers RN; Jacobs HT; Kajander OA, 1999. Mitochondrial DNA--all things bad?  Trends Genet 15(3):91-3

Clark KM; Taylor RW; Johnson MA; Chinnery PF; Chrzanowska-Lightowlers ZM; Andrews RM; Nelson IP; Wood NW; Lamont PJ; Hanna MG; Lightowlers RN; Turnbull DM, 1999. An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy.  Am J Hum Genet 64(5):1330-9

Chrzanowska-Lightowlers ZM; Temperley RJ; McGregor A; Bindoff LA; Lightowlers RN, 1999. Conversion of a reporter gene for mitochondrial gene expression using iterative mega-prime PCR.  Gene 230(2):241-7

Chinnery PF; Zwijnenburg PJ; Walker M; Howell N; Taylor RW; Lightowlers RN; Bindoff L; Turnbull DM, 1999. Nonrandom tissue distribution of mutant mtDNA.  Am J Med Genet 85(5):498-501

Andrews RM; Kubacka I; Chinnery PF; Lightowlers RN; Turnbull DM; Howell N, 1999. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.  Nat Genet 23(2):147

Chinnery PF; Taylor RW; Diekert K; Lill R; Turnbull DM; Lightowlers RN, 1999. Peptide nucleic acid delivery to human mitochondria.  Gene Ther 6(12):1919-28

Brierley EJ; Johnson MA; Lightowlers RN; James OF; Turnbull DM, 1998. Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.  Ann Neurol 43(2):217-23

Chinnery PF; Howell N; Lightowlers RN; Turnbull DM, 1998. MELAS and MERRF. The relationship between maternal mutation load and the frequency of clinically affected offspring.  Brain 121 ( Pt 10):1889-94

Turnbull DM; Lightowlers RN, 1998. An essential guide to mtDNA maintenance.  Nat Genet 18(3):199-200

Chinnery PF; Howell N; Lightowlers RN; Turnbull DM, 1998. Genetic counseling and prenatal diagnosis for mtDNA disease.  Am J Hum Genet 63(6):1908-11

Clark KM; Watt DJ; Lightowlers RN; Johnson MA; Relvas JB; Taanman JW; Turnbull DM, 1998. SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects.  J Clin Invest 102(12):2090-5

Chinnery PF; Johnson MA; Taylor RW; Lightowlers RN; Turnbull DM, 1997. A novel mitochondrial tRNA phenylalanine mutation presenting with acute rhabdomyolysis.  Ann Neurol 41(3):408-10

Adams PL; Lightowlers RN; Turnbull DM, 1997. Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome.  Ann Neurol 41(2):268-70

Taylor RW; Chinnery PF; Turnbull DM; Lightowlers RN, 1997. Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids.  Nat Genet 15(2):212-5

Taylor RW; Chinnery PF; Clark KM; Lightowlers RN; Turnbull DM, 1997. Treatment of mitochondrial disease.  J Bioenerg Biomembr 29(2):195-205

Preiss T; Chrzanowska-Lightowlers ZM; Lightowlers RN, 1997. Glutamate dehydrogenase: an organelle-specific mRNA-binding protein.  Trends Biochem Sci 22(8):290

Lightowlers RN; Chinnery PF; Turnbull DM; Howell N, 1997. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease.  Trends Genet 13(11):450-5

Bidooki SK; Johnson MA; Chrzanowska-Lightowlers Z; Bindoff LA; Lightowlers RN, 1997. Intracellular mitochondrial triplasmy in a patient with two heteroplasmic base changes.  Am J Hum Genet 60(6):1430-8

Chinnery PF; Howell N; Lightowlers RN; Turnbull DM, 1997. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes.  Brain 120 ( Pt 10):1713-21

Clark KM; Bindoff LA; Lightowlers RN; Andrews RM; Griffiths PG; Johnson MA; Brierley EJ; Turnbull DM, 1997. Reversal of a mitochondrial DNA defect in human skeletal muscle.  Nat Genet 16(3):222-4

Lightowlers RN; Sang AE; Preiss T; Chrzanowska-Lightowlers ZM, 1996. Targeting proteins to mitochondria: is there a role for mRNA localization?  Biochem Soc Trans 24(2):527-31

Morris AA; Taylor RW; Lightowlers RN; Aynsley-Green A; Bartlett K; Turnbull DM, 1995. Medium chain acyl-CoA dehydrogenase deficiency caused by a deletion of exons 11 and 12.  Hum Mol Genet 4(4):747-9

Preiss T; Lowerson SA; Weber K; Lightowlers RN, 1995. Human mitochondria: distinct organelles or dynamic network?  Trends Genet 11(6):211-2

Preiss T; Sang AE; Chrzanowska-Lightowlers ZM; Lightowlers RN, 1995. The mRNA-binding protein COLBP is glutamate dehydrogenase.  FEBS Lett 367(3):291-6

Chrzanowska-Lightowlers ZM; Lightowlers RN; Turnbull DM, 1995. Gene therapy for mitochondrial DNA defects: is it possible?  Gene Ther 2(5):311-6

Chrzanowska-Lightowlers ZM; Preiss T; Lightowlers RN, 1994. Inhibition of mitochondrial protein synthesis promotes increased stability of nuclear-encoded respiratory gene transcripts.  J Biol Chem 269(44):27322-8

Preiss T; Chrzanowska-Lightowlers ZM; Lightowlers RN, 1994. The tissue-specific RNA-binding protein COLBP is differentially regulated during myogenesis.  Biochim Biophys Acta 1221(3):286-9

Schillace R; Preiss T; Lightowlers RN; Capaldi RA, 1994. Developmental regulation of tissue-specific isoforms of subunit VIa of beef cytochrome c oxidase.  Biochim Biophys Acta 1188(3):391-7

Lightowlers RN, 1993. Neurologic complications of inherited mitochondrial abnormality, and neurologic consequences of inborn errors of metabolism.  Curr Opin Neurol Neurosurg 6(3):429-36

Sadlock JE; Lightowlers RN; Capaldi RA; Schon EA, 1993. Isolation of a cDNA specifying subunit VIIb of human cytochrome c oxidase.  Biochim Biophys Acta 1172(1-2):223-5

Preiss T; Lightowlers RN, 1993. Post-transcriptional regulation of tissue-specific isoforms. A bovine cytosolic RNA-binding protein, COLBP, associates with messenger RNA encoding the liver-form isopeptides of cytochrome c oxidase.  J Biol Chem 268(14):10659-67

Bindoff LA; Howell N; Poulton J; McCullough DA; Morten KJ; Lightowlers RN; Turnbull DM; Weber K, 1993. Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism.  J Biol Chem 268(26):19559-64

Preiss T; Hall AG; Lightowlers RN, 1993. Identification of bovine glutamate dehydrogenase as an RNA-binding protein.  J Biol Chem 268(33):24523-6

Chrzanowska-Lightowlers ZM; Turnbull DM; Bindoff LA; Lightowlers RN, 1993. An antisense oligodeoxynucleotide approach to investigate the function of the nuclear-encoded subunits of human cytochrome c oxidase.  Biochem Biophys Res Commun 196(1):328-35

Chrzanowska-Lightowlers ZM; Turnbull DM; Lightowlers RN, 1993. A microtiter plate assay for cytochrome c oxidase in permeabilized whole cells.  Anal Biochem 214(1):45-9

Lightowlers RN, 1992. Hereditary disorders including mitochondrial diseases.  Curr Opin Neurol Neurosurg 5(3):368-74

Howitt SM; Lightowlers RN; Gibson F; Cox GB, 1990. Mutational analysis of the function of the a-subunit of the F0F1-APPase of Escherichia coli.  Biochim Biophys Acta 1015(2):264-8

Lightowlers RN; Capaldi RA, 1989. Nucleotide sequence of the cDNA encoding subunit AED (VIB) of beef heart cytochrome c oxidase.  Nucleic Acids Res 17(14):5845

Lightowlers RN; Howitt SM; Hatch L; Gibson F; Cox G, 1988. The proton pore in the Escherichia coli F0F1-ATPase: substitution of glutamate by glutamine at position 219 of the alpha-subunit prevents F0-mediated proton permeability.  Biochim Biophys Acta 933(2):241-8

Lightowlers RN; Howitt SM; Hatch L; Gibson F; Cox GB, 1987. The proton pore in the Escherichia coli F0F1-ATPase: a requirement for arginine at position 210 of the a-subunit.  Biochim Biophys Acta 894(3):399-406

Publication list retrieved from NCBI using ImpactPubs

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