The electrochemical transmission in I-Band segments of the mitochondrial reticulum

• Published in: Biochimica et biophysica acta Vol. 1857; no. 8; pp. 1284 - 1289
• Main Authors: Patel, Keval D., Glancy, Brian, Balaban, Robert S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2016
• Subjects: Adenosine Triphosphate - biosynthesis; Animals; Antiporters; Cations; Cations, Monovalent; Computer Simulation; Diffusion; Finite Element Analysis; Hydrogen-Ion Concentration; Ion Transport; Kinetics; Mice; Mitochondria; Mitochondria reticulum; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - ultrastructure; Models, Biological; Muscle, Skeletal - metabolism; Oxidative Phosphorylation; Oxygen Consumption; Potassium - metabolism; Proton-Motive Force; Protons; Sodium - metabolism; Protons; Mitochondria; Cations; Diffusion; Antiporters; Mitochondria reticulum
• ISSN: 0005-2728; 0006-3002; 1879-2650; 1878-2434
• DOI: 10.1016/j.bbabio.2016.02.014

Within the mitochondrial reticulum of skeletal muscle, the I-Band segments (IBS) traverse the cell and form a contiguous matrix with the mitochondrial segments at the periphery (PS) of the cell. A tight electrical coupling via the matrix between the PS and IBS has been demonstrated. In addition, oxidative phosphorylation complexes that generate the proton motive force (PMF) are preferentially located in the PS, while Complex V, which utilizes the PMF, is primarily located along the IBS. This has led to the hypothesis that PS can support the production of ATP in the IBS by maintaining the potential energy available to produce ATP deep in the muscle cell via conduction of the PMF down the IBS. However, the mechanism of transmitting the PMF down the IBS is poorly understood. This theoretical study was undertaken to establish the physical limits governing IBS conduction as well as potential mechanisms for balancing the protons entering the matrix along the IBS with the ejection of protons in the PS. The IBS was modeled as a 300nm diameter, water-filled tube, with an insulated circumferential wall. Two mechanisms were considered to drive ion transport along the IBS: the electrical potential and/or concentration gradients between the PS to the end of the IBS. The magnitude of the flux was estimated from the maximum ATP production rate for skeletal muscle. The major transport ions in consideration were H+, Na+, and K+ using diffusion coefficients from the literature. The simulations were run using COMSOL Multiphysics simulator. These simulations suggest conduction along the IBS via H+ alone is unlikely requiring un-physiological gradients, while Na+ or K+ could carry the current with minor gradients in concentration or electrical potential along the IBS. The majority of conduction down the IBS is likely dependent on these abundant ions; however, this presents a question as to how H+ is recycled from the matrix of the IBS to the PS for active extrusion. We propose that the abundant cation–proton antiporter in skeletal muscle mitochondria operates in opposite directions in the IBS and PS to permit local recycling of H+ at each site driven by cooperative gradients in H+ and Na+/K+ which favor H+ entry in the PS and H+ efflux in the IBS. This article is part of a Special Issue entitled ‘EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2–6, 2016,’ edited by Prof. Paolo Bernardi. [Display omitted] •Muscle cell mitochondrial reticulum (MR) distributes the proton motive force (PMF).•The MR I-Band segments (IBS) are major distribution pathways for PMF.•Simulations reveal H+ diffusion in IBS is inadequate to support maximum respiration.•Na+ and/or K+ diffusion in IBS can distribute PMF at maximum respiration.•We propose local H+ recycling via cation-H+ antiporters for PMF production and use.