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Regulation of Ca2+-ATPases,V-ATPases and F-ATPases pp 407–437Cite as

The Vacuolar Proton ATPase (V-ATPase): Regulation and Therapeutic Targeting

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

Abstract

V-ATPases are highly conserved proton pumps that are found in all eukaryotic cells. They play vital housekeeping roles in cell physiological processes by performing their classical functions in acidifying luminal compartments of a variety of endomembrane organelles. Recently, it has become evident that V-ATPases also have nonclassical roles that require their direct interaction, apart from their proton translocating function. Moreover, V-ATPases can have specialized tissue-specific functions in organisms, where V-ATPase mutations or inappropriate expression can result in pathological conditions. Because of their multi-subunit structure and numerous subunit variants, V-ATPase expression and function may be uniquely fine-tuned for specific, biologically significant roles. From an interventionist point of view, these same traits potentially make V-ATPases uniquely selectively targetable, both within an organism and among different species. Recent examples, that have at least provided proof of principle for this notion, span fields ranging from medicine to agriculture. The study of V-ATPases in the last three decades has produced thousands of publications and many dozens of review articles. The present work seeks to provide a concise overview of the more recent works on structure and function of V-ATPases, their occurrence and importance, how they are regulated, and how they might be targeted. We focus on recent primary literature, but historical papers of interest and important reviews are also cited. In the areas of targeted pharmaceutical and pesticidal intervention we present published strategies for drug discovery and also provide relevant proofs of concept for targeting V-ATPases to the benefit human health and prosperity.

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Acknowledgements

The authors wish to acknowledge research funding from the Canadian Institutes of Health Research (CIHR). The authors declare no conflict of interest.

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  1. Dental Research Institute, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, Canada, M5G 1G6

    Norbert Kartner & Morris F. Manolson

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Correspondence to Morris F. Manolson .

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  1. Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. University of Manitoba, Institute of Cardiovascular Science St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

    Naranjan S Dhalla

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Kartner, N., Manolson, M.F. (2016). The Vacuolar Proton ATPase (V-ATPase): Regulation and Therapeutic Targeting. 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_20

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