Judy Hirst, Professor of Biological Chemistry at the MRC Mitochondrial Biology Unit, Cambridge, has had a definitive hand in every advance towards defining the highly complex mechanism of complex I catalysis, and has developed new physical and biochemical methods to address the elusive coupling mechanism between the redox reaction and proton translocation. She established the mechanism of complex I inhibition by the anti-diabetic drug metformin, and has used kinetic and thermodynamic strategies to define how superoxide production by complex I, responds to the intramitochondrial NADH/NAD+ ratio to directly link two pathological effects of complex I dysfunction. This seminal work has brought understanding that is fundamental to critical issues of health and disease on a global stage.