The physiological role of complex V in ATP synthesis: Murzyme functioning is viable whereas rotary conformation change model is untenable

Abstract

Complex V or F_oF₁-ATPase is a multimeric protein found in bioenergetic membranes of cells and organelles like mitochondria/chloroplasts. The popular perception on Complex V deems it as a reversible molecular motor, working bi-directionally (breaking or making ATP) via a conformation-change based chemiosmotic rotary ATP synthesis (CRAS) mechanism, driven by proton-gradients or trans-membrane potential (TMP). In continuance of our pursuits against the CRAS model of cellular bioenergetics, herein we demonstrate the validity of the murburn model based in diffusible reactive (oxygen) species (DRS/DROS). Supported by new in silico derived data (that there are ∼12 adenosine nucleotide binding sites on the F₁ bulb and not merely 3 sites, as perceived earlier), available structural information, known experimental observations, and thermodynamic/kinetic considerations (that de-solvation of protons from hydronium ions is facile), we deduce that Complex V serves as a physiological chemostat and a murzyme (enzyme working via murburn scheme, employing DRS). That is- Complex V uses ATP (via consumption at ε or proteins of F₁ module) as a Michaelis-Menten substrate to serve as a pH-stat by inletting protons via the c-ring of F_o module. Physiologically, Complex V also functions as a murzyme by presenting ADP/Pi (or their reaction intermediates) on the αβ bulb, thereby enabling greater opportunities for DRS/proton-assisted ATP formation. Thus, the murburn paradigm succeeds the CRAS hypothesis for explaining the role of oxygen in mitochondrial physiologies of oxidative phosphorylation, thermogenesis, TMP and homeostasis.

Communicated by Ramaswamy H. Sarma

Keywords:

• ATPase
• ATPsynthase
• rotary enzyme
• molecular motor
• Complex V
• bioenergetic phosphorylation
• murzyme
• murburn concept

Acknowledgments

The work was powered by Satyamjayatu: The Science & Ethics Foundation.

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No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Authors’ contributions

KMM conceived the issues/solutions and wrote the first draft of the paper. Abhinav Parashar carried out the structural explorations and in silico analysis. NMB computed the thermodynamic constants of proton-based cations. HT and LJ contributed crucial arguments, inputs and literature.

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Ethics approval and consent to participate

The article is an analytical review of published material, and also has in silico experiments/data, which do not require any experimental procedures with living cells or organisms. Therefore, ethics approval or participation consent is not relevant.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.