- R2RL24, John Bull Building, Plymouth Science Park, Plymouth, PL6 8BU
- charles.affourtit@plymouth.ac.uk
Profiles
Dr Charles Affourtit
Associate Professor (Reader) in Mitochondrial Biology
School of Biomedical Sciences (Faculty of Health)
Biography
Biography
Research
Mitochondrial Biology
Current lab members
Current lab members
Dr Helen McKenna - Academic Clinical Fellow
Past lab members
Dr Rosie Donnell - PhD Student
Dr Jane Carre - Research Fellow (now University of Plymouth)
Mr Anthony Wynne - Research Associate (now Stericycle)
Dr Raid Nisr - Research Associate (now University of Dundee)
Dr Verena Hirschberg Jensen - Research Associate (now University of Copenhagen)
Dr Jonathan Barlow - PhD Student (now University of Birmingham)
Mr Hubert Bieluczyk - Research Associate (now The Pensions Regulator)
Mr Ben Alberts - Research Associate (now Oxford Biomedica)
Mr Joshua Reed - Summer Student (now Swansea University)
Teaching
Module Leader (BHCS1003 - Human Metabolism)
Module Leader (BHCS1003 - Human Metabolism)
Lecturer (Foundation, Stages 1-3)
Personal Tutor
Dissertation Project Advisor
Qualifications
Positions
University of Plymouth
- Associate Head of School (Research), Feb 2023 -
- Associate Professor 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
- Investigative Scientist with Professor Martin Brand, 2004-2009
- Post-Doctoral Research Associate with Professor Tony Moore, 1999-2004
Degrees
- PGCert in Academic Practice, University of 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
Roles on external bodies
Editorial Boards
- Frontiers in Physiology: Mitochondrial Research (Review Editor)
- Frontiers in Physiology: Striated Muscle Physiology (Review Editor)
- Frontiers in Genetics (Guest Associate Editor)
- Physiological Reports
Key publications
(2019) 'Mitochondrial Activity and Skeletal Muscle Insulin Resistance in Kidney Disease' International Journal of Molecular Sciences 20, (11) 2751-2751 , DOI Open access
(2018) 'Control of pancreatic β-cell bioenergetics' Biochemical Society Transactions , DOI Open access
(2016) 'Mitochondrial involvement in skeletal muscle insulin resistance – a case of imbalanced bioenergetics' BBA - Bioenergetics , DOI Open access
(2015) 'Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets' Biochemical Journal 473, (4) 487-496 , DOI Open access
(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 , DOI Open access
(2006) 'Stronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria' Biochem J 393, (Pt 1) 151-159 , DOI
Teaching
Teaching
Teaching interests
- Cellular bioenergetics
- Mitochondrial physiology
- Redox biology
- Metabolism
- Biochemistry
- Metabolic control and regulation
- Biochemical basis of disease
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 engages actively with undergraduate (summer, placement and dissertation projects) and postgraduate (PhD and MSc projects) students to prepare them for independent research careers.
Staff serving as external examiners
Research Degrees
- University of East Anglia (DPhil, 2022)
- University of Dundee (DPhil, 2020)
- La Trobe University, Melbourne, Australia (DPhil, 2018)
- King’s College London (DPhil, 2015)
- Nottingham University (MPhil, 2015)
- University of Northampton (DPhil, 2013)
Research
Research
Research interests
Generally, I am intrigued 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. As detailed in the reviews listed below, my current projects focus on the bioenergetics of (1) insulin secretion by pancreatic beta cells (2) obesity-related and (3) uraemic insulin resistance of skeletal muscle, and (4) dietary-nitrate-enhanced skeletal muscle function.
(1) Affourtit, C. Alberts, B., Barlow, J., Carré, J. E. and Wynne, A. G. (2018) Control of pancreatic beta cell bioenergetics. Biochemical Society Transactions, https://doi.org/10.1042/BST20170505
(2) Affourtit, C. (2016) Mitochondrial involvement in skeletal muscle insulin resistance - a case of imbalanced bioenergetics. BBA – Bioenergetics 1857, 1678-1693. http://dx.doi.org/10.1016/j.bbabio.2016.07.008
(3) Carré, J. E. and Affourtit, C. (2019) Mitochondrial activity and skeletal muscle insulin resistance in kidney disease. International Journal of Molecular Sciences 20, 2751. https://doi.org/10.3390/ijms20112751
(4) Affourtit, C., Bailey, S. J., Jones, A. M., Smallwood, M. J. and Winyard, P. G. (2015) On the mechanism by which dietary nitrate improves human skeletal muscle function. Frontiers in Physiology 6:211. http://dx.doi.org/10.3389/fphys.2015.00211
Research degrees awarded to supervised students
Dr Rosie Donnell (PhD, 2022) - Nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis
Dr Jonathan Barlow (PhD, 2015) - Mitochondrial involvement in pancreatic beta cell glucolipotoxicity
Grants & contracts
Mitochondrial biogenesis and cellular bioenergetic function in uraemic myopathy
Daphne Jackson Trust Fellowship supported by Kidney Research UK (Dr Jane Carre)
March 2019 - May 2021
Total value: £120K
IP Commercialisation Committee (PUPSMD) - Proof-of-Concept funding
November 2017 - March 2019
Total value: £99K
Unravelling the mechanism by which dietary nitrate improves human skeletal muscle function
University of Plymouth (PUPSMD) - PhD Studentship
October 2017 - September 2020
University of Plymouth (PUPSMD) - PhD Studentship
October 2017 - September 2020
Total value: £60K
Nitrate and mitochondrial function
Toxicant-induced synaptic dysfunction and neurotoxicity in Parkinson's disease
Daphne Jackson Trust Fellowship supported by the BBSRC (Mr Anthony Wynne)
November 2015 - October 2017
Total value: £120K
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)
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
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
Publications
Publications
Key publications
(2019) 'Mitochondrial Activity and Skeletal Muscle Insulin Resistance in Kidney Disease' International Journal of Molecular Sciences 20, (11) 2751-2751 , DOI Open access
(2018) 'Control of pancreatic β-cell bioenergetics' Biochemical Society Transactions , DOI Open access
(2016) 'Mitochondrial involvement in skeletal muscle insulin resistance – a case of imbalanced bioenergetics' BBA - Bioenergetics , DOI Open access
(2015) 'Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets' Biochemical Journal 473, (4) 487-496 , DOI Open access
(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 , DOI Open access
(2006) 'Stronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria' Biochem J 393, (Pt 1) 151-159 , DOI
Key publications are highlighted
Journals
Articles
(2022) 'Nitrite lowers the oxygen cost of ATP supply in cultured skeletal muscle cells by stimulating the rate of glycolytic ATP synthesis' PLoS ONE 17, (8) e0266905-e0266905 , DOI Open access
(2022) 'Acute bioenergetic insulin sensitivity of skeletal muscle cells: ATP-demand-provoked glycolysis contributes to stimulation of ATP supply' Biochemistry and Biophysics Reports 30, , DOI Open access
(2021) 'Respiratory Parameters for the Classification of Dysfunctional Insulin Secretion by Pancreatic Islets' Metabolites 11, (6) 405-405 , DOI Open access
(2019) 'Mitochondrial Activity and Skeletal Muscle Insulin Resistance in Kidney Disease' International Journal of Molecular Sciences 20, (11) 2751-2751 , DOI Open access
(2018) 'Pro-inflammatory cytokines attenuate glucose-stimulated insulin secretion from INS-1E insulinoma cells by restricting mitochondrial pyruvate oxidation capacity - Novel mechanistic insight from real-time analysis of oxidative phosphorylation' PLoS One 13, (6) e0199505-e0199505 , DOI Open access
(2018) 'Measurement of Proton Leak in Isolated Mitochondria' Methods in Molecular Biology 1782, 157-170 , DOI Open access
(2018) 'Control of pancreatic β-cell bioenergetics' Biochemical Society Transactions , DOI Open access
(2017) 'Direct Substrate Delivery into Mitochondrial-Fission Deficient Pancreatic Islets Rescues Insulin Secretion' Diabetes db161088-db161088 , DOI Open access
(2016) 'Palmitate-induced changes in energy demand cause reallocation of ATP supply in rat and human skeletal muscle cells' Biochimica et biophysica acta 1857, (9) 1403-1411 , DOI Open access
(2016) 'Mitochondrial coupling efficiency predicts insulin secretion and classifies dysfunctional properties in pancreatic beta cells' Biochimica et Biophysica Acta (BBA) - Bioenergetics 1857, e95-e95 , DOI
(2016) 'Nitrite acutely improves mitochondrial coupling efficiency of spontaneously contracting rat myotubes' Biochimica et Biophysica Acta (BBA) - Bioenergetics 1857, e32-e33 , DOI
(2016) 'Palmitate-induced insulin resistance in rat and human skeletal muscle cells associates with inhibited ATP turnover' Biochimica et Biophysica Acta (BBA) - Bioenergetics 1857, e98-e98 , DOI
(2016) 'Mitochondrial involvement in skeletal muscle insulin resistance – a case of imbalanced bioenergetics' BBA - Bioenergetics , DOI Open access
(2015) 'Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets' Biochemical Journal 473, (4) 487-496 , DOI Open access
(2015) 'On the mechanism by which dietary nitrate improves human skeletal muscle function' Frontiers in Physiology 6, , DOI Open access
(2015) 'Mitochondrialuncouplingprotein-2isnotinvolvedin
palmitate-induced impairmentofglucose-stimulatedinsulinsecretion
in INS-1Einsulinomacellsandisnotneededfortheamplification of
insulin release' Biochemistry and Biophysics Reports 1, 8-15 , DOI Open access
(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 , DOI Open access
(2014) 'Uncoupling protein-2 dampens palmitate-induced mitochondrial reactive oxygen species in INS-1E insulinoma cells' Biochimica et Biophysica Acta (BBA) - Bioenergetics 1837, e35-e35 , DOI
(2014) 'Uncoupling protein-2 does not mediate palmitate-induced glucolipotoxic defects in oxidative phosphorylation in INS-1E insulinoma cells' Biochimica et Biophysica Acta (BBA) - Bioenergetics 1837, e35-e36 , DOI
(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 , DOI Open access
(2013) 'Novel insights into pancreatic β-cell glucolipotoxicity from real-time functional analysis of mitochondrial energy metabolism in INS-1E insulinoma cells' Biochem J 456, (3) 417-426 , DOI Open access
(2013) 'Measuring mitochondrial uncoupling protein-2 level and activity in insulinoma cells' Methods Enzymol 528, 257-267 , DOI
(2012) 'Measurement of proton leak and electron leak in isolated mitochondria' Methods Mol Biol 810, 165-182 , DOI
(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 , DOI Open access
(2010) 'Interaction of purified alternative oxidase from thermogenic Arum maculatum with pyruvate' FEBS Lett 585, (2) 397-401 , DOI
(2010) 'Mitochondrial uncoupling protein 2 in pancreatic β-cells' Diabetes Obes Metab 12 Suppl 2, 134-140 , DOI
(2010) 'Kinetic action and interaction of mitochondrial respiratory enzymes'
(2010) 'Mutagenesis of the Sauromatum guttatum alternative oxidase reveals features important for oxygen binding and catalysis' Biochim Biophys Acta 1797, (6-7) 732-737 , DOI
(2009) 'Measuring mitochondrial bioenergetics in INS-1E insulinoma cells' Methods Enzymol 457, 405-424 , DOI
(2008) 'Dynamic regulation of uncoupling protein 2 content in INS-1E insulinoma cells' Biochim Biophys Acta 1777, (10) 1378-1383 , DOI
(2008) 'Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria' Biochem J 412, (1) 131-139 , DOI Open access
(2008) 'Compelling EPR evidence that the alternative oxidase is a diiron carboxylate protein' Biochim Biophys Acta 1777, (4) 327-330 , DOI
(2008) 'On the role of uncoupling protein-2 in pancreatic beta cells' Biochim Biophys Acta 1777, (7-8) 973-979 , DOI
(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 , DOI
(2007) 'Identification of a mitochondrial alcohol dehydrogenase in Schizosaccharomyces pombe: new insights into energy metabolism' Biochem J 401, (2) 459-464 , DOI
(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 , DOI
(2007) 'Novel uncoupling proteins' Novartis Found Symp 287, 70-80
(2006) 'Stronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria' Biochem J 393, (Pt 1) 151-159 , DOI
(2004) '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 , DOI
(2004) 'Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins' Free Radic Biol Med 37, (6) 755-767 , DOI
(2004) 'Purification of the plant alternative oxidase from Arum maculatum: measurement, stability and metal requirement' Biochim Biophys Acta 1608, (2-3) 181-189 , DOI
(2002) 'Function of the alternative oxidase: is it still a scavenger?' Trends Plant Sci 7, (11) 478-481 , DOI
(2002) 'Control of electron transfer in <i>Schizosaccharomyces pombe</i> mitochondria' Biochemical Society Transactions 30, (1) A30-A30 , DOI
(2002) 'Exploring the molecular nature of alternative oxidase regulation and catalysis' FEBS Lett 510, (3) 121-126 , DOI
(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 , DOI
(2001) 'The effect of Y253F on the activity of the plant alternative oxidase in <i>Schizosaccharomyces pombe</i> mitochondria' Biochemical Society Transactions 29, (5) A123-A123 , DOI
(2001) 'New insights into the regulation of plant succinate dehydrogenase. On the role of the protonmotive force' J Biol Chem 276, (35) 32567-32574 , DOI
(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 , DOI
(2000) 'Maesaquinone: a novel inhibitor of plant mitochondrial respiratory enzymes that react with ubiquinone' IUBMB Life 49, (6) 533-537 , DOI
(1999) 'Functional expression of the plant alternative oxidase affects growth of the yeast Schizosaccharomyces pombe' J Biol Chem 274, (10) 6212-6218 , DOI
(1998) 'A highly conserved glutamate residue (Glu-270) is essential for plant alternative oxidase activity' J Biol Chem 273, (46) 30301-30305 , DOI
(1998) 'Oxygen protection of nitrogen fixation in free-living Azorhizobium caulinodans: the role of cytochrome aa(3)' MICROBIOLOGY-UK 144, 1773-1782 , DOI
(1997) 'Kinetic interaction between oxidases and dehydrogenases in plant mitochondria' Biochem Soc Trans 25, (1) , DOI
(1996) 'Developmental regulation of respiratory activity and protein import in plant mitochondria' Biochem Soc Trans 24, (3) 746-749 , DOI
(1995) 'The relationship between the in situ reduction level of the cytochrome pool of growing in a chemostat with NH or N as the N source and the total activity of cytochrome oxidases' FEMS Microbiology Letters 129, (2-3) 149-155 , DOI
(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
Conference Papers
(2015) 'Palmitate-induced impairment of glucose-stimulated insulin secretion by pancreatic beta cells is disconnected from concomitant mitochondrial respiratory defects' S228-S229 Open access
(2007) 'Novel uncoupling proteins' 70-80
(2006) 'Control of ATP/ADP in pancreatic beta cells: The importance of mitochondrial proton leak' 355-356
(2004) 'Interrelationships between membrane potential, Q-pool redox poise and oxygen consumption rate in potato and yeast mitochondria' 173-173
(2004) 'Kinetic studies on the purifed alternative oxidase protein from Arum maculatum and its regulation by organic acids' 163-163
(2004) 'Regulation of the plant alternative oxidase by pyruvate' 164-164
(2000) 'The active site of the plant alternative oxidase: structural and mechanistic considerations' 31-38
(1999) 'Insights into the active site of the plant alternative oxidase and its relationship to function' 17-36
(1998) 'Over-expression of the mitochondrial matrix located HSP70 in transgenic tobacco results in enhanced growth characteristics' 211-217
Presentations and posters
'Measuring real-time bioenergetic behaviour of electrically stimulated muscle cells' , DOI
'Nitrite lowers the oxygen cost of ATP supply in skeletal muscle cells by stimulating the rate of glycolytic ATP synthesis' , DOI
'Investigation of microbiome metabolites and mitochondrial function in non-alcoholic fatty liver disease' , DOI
Other Publications
(2017) Erratum. Direct Substrate Delivery Into Mitochondrial Fission–Deficient Pancreatic Islets Rescues Insulin Secretion. Diabetes 2017;66:1247–1257. American Diabetes Association , DOI Open access
Personal
Personal
Reports & invited lectures
Lectures
Division of Cell Signalling and Immunology, University of Dundee (2019)
British Association for the Study of the Liver, Annual Basic Science Retreat (2019)
Division of Diabetes and Nutritional Sciences, King’s College London (2019)
MitOX Meeting, University of Oxford (2017)
University of Exeter Medical School, University of Exeter, UK (2017)
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, UK (2016)
Other academic activities
Peer Review
Funding bodies: MRC, BBSRC, Wellcome Trust, Diabetes UK, Great Ormond Street Hospital Children’s Charity, The Physiological Society, Austrian Science Council, Czech Science Foundation, The Netherlands Organisation for Health Research and Development.
Journals: since July 2011, I have provided 212 pre-publication reviews for 57 journals including Nature, Cell Metabolism, Diabetes, and Journal of Biological Chemistry.
Full statistics: https://publons.com/author/1302470/charles-affourtit#stats
Committee
Athena Swan Self-Assessment Team, Faculty of Health, University of Plymouth