Former Guest Editor (up to July 2008)
Dr. Reuven Tirosh
The Biophysical Schottenstein Center, Physics Department, Bar Ilan University, Ramat-Gan 52900, Israel; E-mail: tiroshr1@mail.biu.ac.il

Dr. Walter Herzog
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Dr. N.W., Calgary, AB T2N 1N4, Canada

Professor Julian Borejdo
Professor of Molecular Biology, Department of Molecular Biology, University of North Texas, Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA

Dr. Valdur Saks
Laboratory of Bioenergetics, INSERM U884, Joseph Fourier University Grenoble, France

Manuscript ID: IJMS-21-05
Type of Paper: Review
Title: Molecular mechanism of the actin-linked regulation of ATPase cycle in various muscle types
Authors: Yuri S. Borovikov, Olga E. Karpicheva and Stanislava V. Avrova
Affiliation: Laboratory of Mechanisms of Cell Motility, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 St. Petersburg, Russia.
Abstract: The data on modulation of the conformational changes in actin and myosin during ATPase cycle by different actin-binding regulatory proteins (tropomyosin, troponin, caldesmon, calponin and twitchin) obtained by the polarized fluorescence technique has been analyzed.  It is supposed that contraction in various muscle types is regulated via universal mechanism lying in disturbing the teamwork of actin and myosin in actomyosin motors.

Type of Paper: Article
Title: Towards a New, Unified Thermodynamic Theory of Oxidative Phosphorylation and Muscle Contraction and Its Manifold Consequences and Applications in Health and Disease
Authors: Sunil Nath
Affiliation: Department of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110106, India
Abstract:  Further fine and intricate details of the thermodynamics and molecular mechanisms of ATP synthesis/hydrolysis and muscle contraction are offered from the standpoint of the torsional mechanism of energy transduction and the rotation-uncoiling-tilt (RUT) energy storage mechanism of muscle contraction (Nath, S., A novel systems biology/engineering approach solves fundamental molecular mechanistic problems in bioenergetics and motility, Process Biochemistry 2006, 41, 2218-2235). In particular, the way in which energy is distributed among and released by the elementary sub-steps of ATP binding, ATP cleavage, and P_i release in the ATP hydrolysis cycle is specified. (For ATP synthesis by F₁F_O-ATP synthase, the same quanta of energies have to be supplied at these elementary steps by an external source). This unified theory is in agreement with every biochemical and biophysical (including single molecule) experiment and represents one and probably the only way to avoid violations of the first and second laws of thermodynamics, extirpate the various inconsistencies in the previous theories, and reconcile the contradictory and often diametrically opposite assumptions made by the bioenergetics and motility research communities. The manifold absolutely fundamental consequences of this specific theory for oxidative phosphorylation and muscle contraction are explained in as concise a way as possible. For instance, for muscle contraction, the picture that emerges is one where the free energy released upon MgATP binding to actomyosin, MgATP bond cleavage on myosin and subsequent Pi release to infinity upon rebinding of myosin to actin (~9 + ~9 + ~18 kJ/mol respectively) is stored in a nonequilibrium conformational state of myosin S-2 with uncoiled first few N-terminal heptads. The thermodynamic propensity of the S-2 coiled coil and especially of its hydrophobic residues to repel water and recoil and regain the more stable resting state of the coiled coil is the true thermodynamic driving force of muscle contraction which allows the two heads of myosin (bound to the same actin or to different actins) to execute their power strokes simultaneously, taking us beyond the lever arm model and rationalizing the double-headed and coiled coil nature of myosin, which had been a longstanding puzzle. A role for anions along with protons in the F_O portion of ATP synthase in oxidative phosphorylation is provided along with new experimental data, and the explanations of the key role of membrane elements in a lipophilic region are made water-tight and go far beyond the chemiosmotic theory which considered these regions merely as ?nsulation material.?Finally the great applications of the unified theory to disease, e.g., to mitochondrial apoptosis and cell death are outlined. It would be quite impossible to address each and every specific aspect above in consummate detail in a paper such as this, but what is presented should be sufficient to convince the reader of the novelty, originality, fundamental nature and power of the unified theory and its manifold applications in health and disease.
 
Type of Paper: Article
Title: Thick filament assembly, maintenance and degradation: Role of the UNC-45 chaperone in myosin thick filament dynamics
Authors: Torah M. Kachur and David B. Pilgrim
Affiliation: University of Alberta, Canada
Abstract: Myofibrillogenesis in striated muscle cells requires a precise ordered pathway to assemble many different proteins into a linear array of sarcomeres.  The contractile sarcomere relies on the interdigitated thick and thin filaments to ensure muscle contraction, and achieving this organization requires a series of protein folding and assembly steps to form the myosin containing thick filaments.  The myosin head domain must be folded into its correct conformation and the myosin molecules must dimerize and assemble into antiparallel and parallel arrays forming the nascent thick filaments.  Finally, the short and incomplete myosin filaments assemble into the long thick filament where it is incorporated into the developing sarcomere.  Once assembled, the myosin undergoes drastic conformation changes during contraction where environmental stresses can cause the myosin head to unfold, and maintenance of the thick filament is required in fully formed sarcomeres.  If the degree of unfolding of myosins within the thick filaments is terminal, the muscle cells must turnover these myosins rapidly and efficiently to ensure the maintenance of myosin contraction.  Myosin folding and sarcomeric assembly requires association of classical chaperones as well as folding cofactors such as UNC-45 that helps fold the complex myosin head domain.  Recent research has indicated that UNC-45 is required beyond initial myosin head folding and is necessary at many different stages of myosin thick filament assembly, maintenance and degradation