Profiles
Dr Charles Affourtit
Associate Professor (Reader) in Mitochondrial Biology
School of Biomedical Sciences (Faculty of Medicine and Dentistry)
Role
Research
Mitochondrial Biology
https://www.plymouth.ac.uk/research/biomedical-research-group/mitochondrial-biology
Current lab members
Dr Jane Carre - Research Associate (Visiting)
Mr Anthony Wynne - Research Fellow
Miss Rosie Donnell - PhD Student
Past lab members
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 University of Plymouth)
Mr Ben Alberts - Research Associate (now University of Sussex)
Mr Joshua Reed - Summer Student (now Swansea University)
Teaching
Module Leader
BHCS1003 - Human Metabolism (Stage 1)
Module Leader
BHCS1003 - Human Metabolism (Stage 1)
Pastoral
Personal Tutor
Biomedical Sciences students
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
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
Measuring the bioenergetics of electrically stimulated skeletal muscle cells
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 (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
Key publications are highlighted
Journals
Articles
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
PEARL
2018
'Measurement of Proton Leak in Isolated Mitochondria'
Methods in Molecular Biology
1782,
157-170
, DOI
PEARL
2017
'Erratum. Direct Substrate Delivery Into Mitochondrial Fission–Deficient Pancreatic Islets Rescues Insulin Secretion. Diabetes 2017;66:1247–1257'
Diabetes
66,
(12)
3144.1-3144
, DOI
2017
'Direct Substrate Delivery into Mitochondrial-Fission Deficient Pancreatic Islets Rescues Insulin Secretion'
Diabetes
db161088-db161088
, DOI
PEARL
2016
'Palmitate-induced changes in energy demand cause reallocation of ATP
supply in rat and human skeletal muscle cells'
BBA Bioenergetics
, DOI
PEARL
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
PEARL
2015
'Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets'
Biochemical Journal
473,
(4)
487-496
, DOI
PEARL
2015
'On the mechanism by which dietary nitrate improves human skeletal muscle function'
Frontiers in Physiology
6,
, DOI
PEARL
2015
'Mitochondrialuncouplingprotein-2isnotinvolvedin
palmitate-induced impairmentofglucose-stimulatedinsulinsecretion
in INS-1Einsulinomacellsandisnotneededfortheamplification of
insulin release'
Biochemistry and Biophysics Reports
1,
8-15
, DOI
PEARL
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
PEARL
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
PEARL
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
PEARL
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
PEARL
2011
'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
'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
'On the role of uncoupling protein-2 in pancreatic beta cells'
Biochim Biophys Acta
1777,
(7-8)
973-979
, DOI
2008
'Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria'
Biochem J
412,
(1)
131-139
, DOI
PEARL
2008
'Compelling EPR evidence that the alternative oxidase is a diiron carboxylate protein'
Biochim Biophys Acta
1777,
(4)
327-330
, 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
'Novel uncoupling proteins'
Novartis Found Symp
287,
70-80
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
2006
'Stronger control of ATP/ADP by proton leak in pancreatic β-cells than skeletal muscle mitochondria'
Biochemical Journal
393,
(1)
151-159
, DOI
2005
'Constitutive activity of Sauromatum guttatum alternative oxidase in Schizosaccharomyces pombe implicates residues in addition to conserved cysteines in α-keto acid activation'
FEBS Letters
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
2002
'Exploring the molecular nature of alternative oxidase regulation and catalysis'
FEBS Lett
510,
(3)
121-126
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
'New insights into the regulation of plant succinate dehydrogenase. On the role of the protonmotive force'
J Biol Chem
276,
(35)
32567-32574
, DOI
2001
'Control of plant mitochondrial respiration'
Biochim Biophys Acta
1504,
(1)
58-69
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
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
1999
'Kinetic action and interaction of mitochondrial respiratory enzymes'
1998
'A highly conserved glutamate residue (Glu-270) is essential for plant alternative oxidase activity'
J Biol Chem
273,
(46)
30301-30305
1998
'Oxygen protection of nitrogen fixation in free-living Azorhizobium caulinodans: the role of cytochrome aa3'
Microbiology
144,
(7)
1773-1782
, DOI
1997
'Kinetic interaction between oxidases and dehydrogenases in plant mitochondria'
Biochem Soc Trans
25,
(1)
1996
'Developmental regulation of respiratory activity and protein import in plant mitochondria'
Biochem Soc Trans
24,
(3)
746-749
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
PEARL
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