He was appointed a research post in the Department of Biochemistry, Cambridge, in 1942, and was awarded aPh.D. in early 1951 for work on the mode of action ofpenicillin.[4]
In 1955 he was invited by ProfessorMichael Swann to set up a biochemical research unit, called the Chemical Biology Unit, in the Department of Zoology, at theUniversity of Edinburgh, where he was appointed a SeniorLecturer in 1961, thenReader in 1962, although institutional opposition to his work coupled with ill health led to his resignation in 1963.[3]
From 1963 to 1965, he supervised the restoration of aRegency-fronted Mansion, known asGlynn House, atCardinham nearBodmin,Cornwall - adapting a major part of it for use as a research laboratory. He and his former research colleague,Jennifer Moyle founded a charitable company, known as Glynn Research Ltd., to promote fundamental biological research at Glynn House and they embarked on a programme of research onchemiosmotic reactions and reaction systems.[5][6][7][8][9]
In the 1960s,ATP was known to be the energy currency of life, but the mechanism by which ATP was created in themitochondria was assumed to be bysubstrate-level phosphorylation. Mitchell'schemiosmotic hypothesis was the basis for understanding the actual process ofoxidative phosphorylation. At the time, the biochemical mechanism of ATP synthesis by oxidative phosphorylation was unknown.
In chemiosmosis, ions move down their electrochemical gradient across a membrane.
Mitchell realised that the movement of ions across anelectrochemical potential difference could provide the energy needed to produce ATP. His hypothesis was derived from information that was well known in the 1960s. He knew that living cells had amembrane potential; interior negative to the environment. The movement of charged ions across a membrane is thus affected by the electrical forces (the attraction of positive to negative charges). Their movement is also affected bythermodynamic forces, the tendency of substances todiffuse from regions of higher concentration. He went on to show that ATP synthesis was coupled to thiselectrochemical gradient.[10]
The discovery of ATP synthase vindicated Mitchell's hypothesis. Today, it is well-accepted that chemiosmosis of H+ ions power the synthesis of ATP, and other biochemical processes.
His hypothesis was confirmed by the discovery ofATP synthase, a membrane-bound protein that uses the potential energy of the electrochemical gradient to make ATP; and by the discovery byAndré Jagendorf that a pH difference across thethylakoid membrane in thechloroplast results in ATP synthesis.[11]
Later, Peter Mitchell also hypothesized some of the complex details of electron transport chains. He conceived of the coupling of proton pumping to quinone-basedelectron bifurcation, which contributes to the proton motive force and thus, ATP synthesis.[12]
^Greville, G.D. (1969). "A scrutiny of Mitchell's chemiosmotic hypothesis of respiratory chain and photosynthetic phosphorylation".Curr. Topics Bioenergetics. Current Topics in Bioenergetics.3:1–78.doi:10.1016/B978-1-4831-9971-9.50008-0.ISBN9781483199719.
^Peter Mitchell on Nobelprize.org, accessed 11 October 2020 including the Nobel Lecture on 8 December 1978David Keilin’s Respiratory Chain Concept and Its Chemiosmotic Consequences
