Dr Charles Affourtit
Profiles

Dr Charles Affourtit

Associate Professor (Reader) in Mitochondrial Biology

School of Biomedical & Healthcare Sciences (Plymouth University Peninsula Schools of Medicine and Dentistry)

Role

Research
                                        Centre for Biomedical Research
                                        http://www1.plymouth.ac.uk/research/crtb/Pages/default.aspx

                                        Current lab members

                                        Dr Jane Carre - Research Fellow (Visiting)
                                        Dr Raid Nisr - Research Fellow (Visiting)
                                        Mr Anthony Wynne - Research Fellow (Daphne Jackson Trust)
                                        Mr Hubert Bieluczyk (MSc student)

                                        Past lab members
                                        Dr Verena Hirschberg Jensen - Research Fellow (MRC)
                                        Dr Jonathan Barlow - PhD Student (Plymouth University)
                                        Mr Ben Alberts - Research Fellow (Work Experience)
                                        Ms Emi-Jo Mawson - Placement Student (Plymouth University)
Teaching
                                        Module Leader
                                        BHCS1003 - Human Metabolism (Stage 1)
                                        BHCS2020 - Human Metabolism (Stage 2)
Pastoral
                                        Personal Tutor
                                        Biomedical Sciences students

Qualifications

Positions
                                        Plymouth University - UK
                                        
Reader in Mitochondrial Biology, 2016-

                                        Lecturer in Biochemistry, 2010-2016

                                        Seahorse Bioscience - Billerica USA
                                        Scientific consultant, 2009-2010

                                        Buck Institute for Age Research - North-Bay Area USA
                                        Visiting Scientist, 2009-2010

                                        MRC Mitochondrial Biology Unit - Cambridge UK
                                        Investigative Scientist with Prof. Martin Brand, 2004-2009

                                        University of Sussex - Brighton UK
                                        Post-Doctoral Research Associate with Prof. Tony Moore, 1999-2004   Degrees
                                        PGCert in Academic Practice
                                        Plymouth University, 2011

                                        DPhil in Biochemistry
                                        
University of Sussex, 2000

                                        MSc in Biology 
                                        
Vrije Universiteit Amsterdam, 1995

Professional membership

Societies
                                        Biochemical Society since 1995

                                        Mitochondrial Physiology Society since 2007

                                        Higher Education Academy since 2012

Teaching interests

Bioenergetics
Biochemical basis of disease 
Metabolic control and regulation
Enzymology

To me, teaching and research are intimately linked activities, as I appreciate the importance of transferring cutting-edge knowledge and, perhaps more importantly, as I wish to inspire and enthuse the next generation of researchers. I currently teach fundamental biochemistry to undergraduates at all stages of various degree programmes and, firmly informed by my research, I show how this basic science underpins the development of metabolic disorders, and how it drives disease diagnosis and management. My lab accommodates many undergraduate students for summer, placement and dissertation projects. If nothing else, the transferable skills gained from such projects are invaluable and greatly enhance student employability. Furthermore, I am keen to engage postgraduate students in my work, and to prepare them for independent research careers.

Research interests

Generally, I am intruiged by the role of bioenergetic failure in disease pathophysiology. In particular, I wish to understand how mitochondrial dysfunction affects glucose-stimulated insulin secretion by pancreatic beta cells and the insulin responsiveness of skeletal muscle. Defects in insulin secretion and action that arise in obesity are both features of the Metabolic Syndrome, a cluster of medical disorders that collectively increase the risk of developing type 2 diabetes. My current projects focus on (1) the physiological role of mitochondrial uncoupling protein-2 in beta cells, (2) mitochondrial involvement in beta cell glucolipotoxicity, (3) the bioenergetics of fatty acid-induced insulin resistance of skeletal muscle, and (4) the effect of dietary nitrate on skeletal muscle function.

Grants & contracts

Unravelling the mechanism by which dietary nitrate improves human skeletal muscle function
University of Plymouth (PUPSMD) - PhD Studentship
October 2016 - September 2019

Total value: £60K

Nitrate and mitochondrial function
Daphne Jackson Trust Fellowship (Mr Anthony Wynne)
November 2015 - October 2017
Total value: £120K

Toxicant-induced synaptic dysfunction and neurotoxicity in Parkinson's disease
National Institutes of Health, USA - Research Project Grant 1R01 ES22274-01A1 (with Kim Tieu (PI) and Robert Fern)
July 2015 - June 2018
Total value: $737K

Manipulating mitochondrial dynamics as a potential therapeutic strategy for Parkinson's disease
Medical Research Council - Research Grant MR/L022079/1 (with Kim Tieu (PI), Robert Fern and Erwan Bezard)
May 2014 - April 2017
Total value: £513K

Why do pancreatic beta cells waste energy?
Medical Research Council - New Investigator Research Grant G1100165/1
February 2012 - April 2016
Total value: £434K

Mitochondrial involvement in pancreatic beta cell lipotoxicity
University of Plymouth (Faculty of Science and Technology) - PhD Studentship
October 2011 - September 2014
Total value: £60K

Key publications are highlighted

Journals
Articles
Barlow J, Hirschberg Jensen V & Affourtit C 2015 'Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells' Redox Biol 4, 14-22 Author Site , DOI
Nisr RB & Affourtit C 2014 'Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation' Biochim Biophys Acta 1837, (2) 270-276 Author Site , DOI
Affourtit C, Quinlan CL & Brand MD 2012 'Measurement of proton leak and electron leak in isolated mitochondria' Methods Mol Biol 810, 165-182 Author Site , DOI
Carré JE, Affourtit C & Moore AL 2011 'Interaction of purified alternative oxidase from thermogenic Arum maculatum with pyruvate' FEBS Lett 585, (2) 397-401 Author Site , DOI
Affourtit C, Jastroch M & Brand MD 2011 'Uncoupling protein-2 attenuates glucose-stimulated insulin secretion in INS-1E insulinoma cells by lowering mitochondrial reactive oxygen species' Free Radic Biol Med 50, (5) 609-616 Author Site , DOI
Brand MD, Parker N, Affourtit C, Mookerjee SA & Azzu V 2010 'Mitochondrial uncoupling protein 2 in pancreatic β-cells' Diabetes Obes Metab 12 Suppl 2, 134-140 Author Site , DOI
Crichton PG, Albury MS, Affourtit C & Moore AL 2010 'Mutagenesis of the Sauromatum guttatum alternative oxidase reveals features important for oxygen binding and catalysis' Biochim Biophys Acta 1797, (6-7) 732-737 Author Site , DOI
Affourtit C & Brand MD 2009 'Measuring mitochondrial bioenergetics in INS-1E insulinoma cells' Methods Enzymol 457, 405-424 Author Site , DOI
Moore AL, Carré JE, Affourtit C, Albury MS, Crichton PG, Kita K & Heathcote P 2008 'Compelling EPR evidence that the alternative oxidase is a diiron carboxylate protein' Biochim Biophys Acta 1777, (4) 327-330 Author Site , DOI
Azzu V, Affourtit C, Breen EP, Parker N & Brand MD 2008 'Dynamic regulation of uncoupling protein 2 content in INS-1E insulinoma cells' Biochim Biophys Acta 1777, (10) 1378-1383 Author Site , DOI
Parker N, Affourtit C, Vidal-Puig A & Brand MD 2008 'Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria' Biochem J 412, (1) 131-139 Author Site , DOI
Affourtit C & Brand MD 2008 'On the role of uncoupling protein-2 in pancreatic beta cells' Biochim Biophys Acta 1777, (7-8) 973-979 Author Site , DOI
Affourtit C & Brand MD 2008 'Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion' Biochem J 409, (1) 199-204 Author Site , DOI
Crichton PG, Affourtit C & Moore AL 2007 'Identification of a mitochondrial alcohol dehydrogenase in Schizosaccharomyces pombe: new insights into energy metabolism' Biochem J 401, (2) 459-464 Author Site , DOI
Affourtit C, Crichton PG, Parker N & Brand MD 2007 'Novel uncoupling proteins' Novartis Found Symp 287, 70-80 Author Site
Covey-Crump EM, Bykova NV, Affourtit C, Hoefnagel MHN, Gardestrom P & Atkin OK 2007 'Temperature-dependent changes in respiration rates and redox poise of the ubiquinone pool in protoplasts and isolated mitochondria of potato leaves' PHYSIOLOGIA PLANTARUM 129, (1) 175-184 Author Site , DOI
Affourtit C & Brand MD 2006 'Stronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria' Biochem J 393, (Pt 1) 151-159 Author Site , DOI
Crichton PG, Affourtit C, Albury MS, Carré JE & Moore AL 2005 'Constitutive activity of Sauromatum guttatum alternative oxidase in Schizosaccharomyces pombe implicates residues in addition to conserved cysteines in alpha-keto acid activation' FEBS Lett 579, (2) 331-336 Author Site , DOI
Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL & Parker N 2004 'Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins' Free Radic Biol Med 37, (6) 755-767 Author Site , DOI
Affourtit C & Moore AL 2004 'Purification of the plant alternative oxidase from Arum maculatum: measurement, stability and metal requirement' Biochim Biophys Acta 1608, (2-3) 181-189 Author Site , DOI
Affourtit C, Albury MS, Crichton PG & Moore AL 2002 'Exploring the molecular nature of alternative oxidase regulation and catalysis' FEBS Lett 510, (3) 121-126 Author Site
Moore AL, Albury MS, Crichton PG & Affourtit C 2002 'Function of the alternative oxidase: is it still a scavenger?' Trends Plant Sci 7, (11) 478-481 Author Site
Albury MS, Affourtit C, Crichton PG & Moore AL 2002 'Structure of the plant alternative oxidase. Site-directed mutagenesis provides new information on the active site and membrane topology' J Biol Chem 277, (2) 1190-1194 Author Site , DOI
Affourtit C, Krab K & Moore AL 2001 'Control of plant mitochondrial respiration' Biochim Biophys Acta 1504, (1) 58-69 Author Site
Affourtit C, Krab K, Leach GR, Whitehouse DG & Moore AL 2001 'New insights into the regulation of plant succinate dehydrogenase. On the role of the protonmotive force' J Biol Chem 276, (35) 32567-32574 Author Site , DOI
Affourtit C, Whitehouse DG & Moore AL 2000 'Maesaquinone: a novel inhibitor of plant mitochondrial respiratory enzymes that react with ubiquinone' IUBMB Life 49, (6) 533-537 Author Site , DOI
Affourtit C, Heaney SP & Moore AL 2000 'Mitochondrial electron transfer in the wheat pathogenic fungus Septoria tritici: on the role of alternative respiratory enzymes in fungicide resistance' Biochim Biophys Acta 1459, (2-3) 291-298 Author Site
Affourtit C, Albury MS, Krab K & Moore AL 1999 'Functional expression of the plant alternative oxidase affects growth of the yeast Schizosaccharomyces pombe' J Biol Chem 274, (10) 6212-6218 Author Site
Albury MS, Affourtit C & Moore AL 1998 'A highly conserved glutamate residue (Glu-270) is essential for plant alternative oxidase activity' J Biol Chem 273, (46) 30301-30305 Author Site
Boogerd FC, Pronk AF, Mashingaidze C, Affourtit C, Stouthamer AH, van Verseveld HW & Westerhoff HV 1998 'Oxygen protection of nitrogen fixation in free-living Azorhizobium caulinodans: the role of cytochrome aa(3)' MICROBIOLOGY-UK 144, 1773-1782 Author Site
Affourtit C, Leach GR, Krab K & Moore AL 1997 'Kinetic interaction between oxidases and dehydrogenases in plant mitochondria' Biochem Soc Trans 25, (1) Author Site
Wood CK, Dudley P, Albury MS, Affourtit C, Leach GR, Pratt JR, Whitehouse DG & Moore AL 1996 'Developmental regulation of respiratory activity and protein import in plant mitochondria' Biochem Soc Trans 24, (3) 746-749 Author Site
PRONK AF, AFFOURTIT C, MASHINGAIDZE C, STOUTHAMER AH, VANVERSEVELD HW & BOOGERD FC 1995 'THE RELATIONSHIP BETWEEN THE IN-SITU REDUCTION LEVEL OF THE CYTOCHROME-C POOL OF AZORHIZOBIUM-CAULINODANS GROWING IN A CHEMOSTAT WITH NH4+ OR N-2 AS THE N-SOURCE AND THE TOTAL ACTIVITY OF CYTOCHROME-C OXIDASES' FEMS MICROBIOLOGY LETTERS 129, (2-3) 149-155 Author Site
Conference Papers
Affourtit C & Brand MD 2008 'Activity of uncoupling protein-2 in pancreatic beta cells' //0 //0 S76-S77 , DOI
Azzu V, Affourtit C, Breen EP, Parker N & Brand MD 2008 'Dynamic regulation of UCP2 concentration in INS-1E pancreatic beta-cells' //0 //0 S77-S77 , DOI
Affourtit C & Brand MD 2006 'Control of ATP/ADP in pancreatic beta cells: The importance of mitochondrial proton leak' //0 //0 355-356
Van Aken AFJ, Affourtit C & Moore AL 2004 'Interrelationships between membrane potential, Q-pool redox poise and oxygen consumption rate in potato and yeast mitochondria' //0 //0 173-173
Carre JE, Affourtit C, Yu F & Moore AL 2004 'Kinetic studies on the purifed alternative oxidase protein from Arum maculatum and its regulation by organic acids' //0 //0 163-163
Crichton PG, Affourtit C, Albury MS, Carre JE & Moore AL 2004 'Regulation of the plant alternative oxidase by pyruvate' //0 //0 164-164
Affourtit C, Albury MS, Whitehouse DG & Moore AL 2000 'The active site of the plant alternative oxidase: structural and mechanistic considerations' //0 //0 31-38
Affourtit C & Moore AL 1999 'Insights into the active site of the plant alternative oxidase and its relationship to function' //0 //0 17-36
Wood CK, Affourtit C, Albury MS, Carre J, Dudley P, Gordon J, Harpham NVJ, Whitehouse DG & Moore AL 1998 'Over-expression of the mitochondrial matrix located HSP70 in transgenic tobacco results in enhanced growth characteristics' //0 //0 211-217