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

Abstract

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 300 nm 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 Multi-physics 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.

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

“…In the classic 2-mitochondrial population model, a collection of peripheral mitochondria has decreased oxidative capacity compared with the physically distinct pool of mitochondria in the myofibrillar space (75)(76)(77). In the newly emerging view of mitochondria, in which mitochondria are thought to exist in a dynamic reticulum extending from the sarcolemma to the myofibrils and actively undergo fusion and fission in continuous networks throughout the cell, peripheral segment mitochondria have a greater abundance of proton motive proteins, whereas the connected intermyofibrillar mitochondria located in the I-band have more ATP-generating proteins for use by sarcomeres (56,78). In the current study, the abnormal spherical mitochondria in the peripheral space of injured muscles at 30 and 60 d after rotator cuff tear could reflect a mitochondrial network that has been mechanically and biochemically disrupted; this is supported by observations in yeast in which the small mitochondria that bud off of larger networks of mitochondria have a spherical appearance (79).…”

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging

“…We note that the observation of lower energetic capacity at the highest levels of demand is more consistent with intrinsic defect in oxidative phosphorylation when challenged above a certain threshold. For example, studies in mice have found that skeletal muscle mitochondria are organized in a highly reticular structure around the myofibrils (Glancy et al., ; Patel, Glancy & Balaban, ; Porter et al., ). Glancy et al.…”

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

“…In the classical two mitochondrial population model, a collection of peripheral mitochondria have decreased oxidative capacity compared to the physically distinct pool of mitochondria in the myofibrillar space (70)(71)(72). In the newly emerging view of mitochondria, where mitochondria are thought to exist in a dynamic reticulum extending from the sarcolemma to the myofibrils, and actively undergoing fusion and fission in continuous networks throughout the cell, peripheral segment mitochondria have a greater abundance of proton motive proteins, whereas the connected intermyofibrillar mitochondria located in the I-band have more ATP generating proteins for use by sarcomeres (51,73). In the current study, the abnormal spherical mitochondria in the peripheral space of injured muscles at 30 and 60 days after rotator cuff tear could reflect a mitochondrial network that has been mechanically and biochemically disrupted, and this is supported from observations in yeast in which the small mitochondria that bud off of larger networks of mitochondria have a spherical appearance (74).…”