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Thiol-Related Regulation of the Mitochondrial F1FO-ATPase Activity

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Regulation of Ca2+-ATPases,V-ATPases and F-ATPases

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 14))

Abstract

The ATP synthase or F1FO-ATPase is the key enzyme in cell bioenergetics, due to its main role to build ATP, but it can also work “in reverse” to hydrolyze ATP. The enzyme complex, increasingly involved as key molecular switch between life and death, is finely tuned by multiple and only partially known mechanisms, widely operative in health and disease. Among them, the enzyme regulation through the chemical modification of protein thiols, namely cysteine side chains, is thought to play a prominent role. Thiols are known to have high biological impact, to be easily oxidized, susceptive to multiple post-translational oxidative modifications and to occur both in the catalytic sector F1 and in the membrane-embedded rotor FO which form the F1FO complex. Even if thiol properties mirror the chemical attitudes of sulfur, not all cysteine thiols are equally prone to chemical modifications, being strongly influenced by their molecular environment. Cysteine thiol modifications, which, according to the ambient, may be reversible, interchangeable and even irreversible, not only modulate the enzyme catalytic and proton channeling activities, but also its response to co-occurring effectors. Additionally, they mirror the ambient redox state and the availability of reactive species involved in cell signaling. In short, within the F1FO complex, thiols act as chemical interface between the environment and the enzyme function. In this chapter the knowledge on the thiol-related F1FO-ATPase modulation is reviewed, with special focus on mammalian mitochondria, aiming at contributing to shed light on a key molecular mechanism under physiological and pathological conditions.

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Work financed by RFO (Fundamental and Oriented Research) grant from the University of Bologna, Italy.

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Correspondence to Alessandra Pagliarani .

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Pagliarani, A., Nesci, S., Trombetti, F., Ventrella, V. (2016). Thiol-Related Regulation of the Mitochondrial F1FO-ATPase Activity. In: Chakraborti, S., Dhalla, N. (eds) Regulation of Ca2+-ATPases,V-ATPases and F-ATPases. Advances in Biochemistry in Health and Disease, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-24780-9_21

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