title: The c-Ring of the F1FO-ATP Synthase: Facts and Perspectives.
abstract: The F1FO-ATP synthase is the only enzyme in nature endowed with bi-functional catalytic mechanism of synthesis and hydrolysis of ATP. The enzyme functions, not only confined to energy transduction, are tied to three intrinsic features of the annular arrangement of c subunits which constitutes the so-called c-ring, the core of the membrane-embedded FO domain: (i) the c-ring constitution is linked to the number of ions (H(+) or Na(+)) channeled across the membrane during the dissipation of the transmembrane electrochemical gradient, which in turn determines the species-specific bioenergetic cost of ATP, the "molecular currency unit" of energy transfer in all living beings; (ii) the c-ring is increasingly involved in the mitochondrial permeability transition, an event linked to cell death and to most mitochondrial dysfunctions; (iii) the c subunit species-specific amino acid sequence and susceptibility to post-translational modifications can address antibacterial drug design according to the model of enzyme inhibitors which target the c subunits. Therefore, the simple c-ring structure not only allows the F1FO-ATP synthase to perform the two opposite tasks of molecular machine of cell life and death, but it also amplifies the enzyme's potential role as a drug target.
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Nesci
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Trombetti
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Ventrella
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy. alessandra.pagliarani@unibo.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pagliarani
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D021122:Protein Subunits; D000255:Adenosine Triphosphate; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Bioenergetic cost; Drug-binding region; F1FO-ATP synthase; Mitochondrial permeability transition; c-Ring, mitochondria