In Vivo Microscopy Reveals Extensive Embedding of Capillaries within the Sarcolemma of Skeletal Muscle Fibers

Abstract

Objective To provide insight into mitochondrial function in vivo, we evaluated the 3D spatial relationship between capillaries, mitochondria, and muscle fibers in live mice. Methods 3D volumes of in vivo murine Tibialis anterior muscles were imaged by multi-photon microscopy (MPM). Muscle fiber type, mitochondrial distribution, number of capillaries, and capillary-to-fiber contact were assessed. The role of myoglobin-facilitated diffusion was examined in myoglobin knockout mice. Distribution of GLUT4 was also evaluated in the context of the capillary and mitochondrial network. Results MPM revealed that 43.6 ± 3.3% of oxidative fiber capillaries had ≥ 50% of their circumference embedded in a groove in the sarcolemma, in vivo. Embedded capillaries were tightly associated with dense mitochondrial populations lateral to capillary grooves and nearly absent below the groove. Mitochondrial distribution, number of embedded capillaries, and capillary-to-fiber contact were proportional to fiber oxidative capacity and unaffected by myoglobin knockout. GLUT4 did not preferentially localize to embedded capillaries. Conclusions Embedding capillaries in the sarcolemma may provide a regulatory mechanism to optimize delivery of oxygen to heterogeneous groups of muscle fibers. We hypothesize that mitochondria locate to paravascular regions due to myofibril voids created by embedded capillaries, not to enhance the delivery of oxygen to the mitochondria.

Power Grid Protection of the Muscle Mitochondrial Reticulum

“…Cardiac mitochondrial network structure was significantly different from the SKM described previously (Glancy et al, 2015). Paravascular mitochondria (PVM, Figure 1D) were much less frequent than in SKM but still associated with shallow capillary grooves (Glancy et al, 2014). Paranuclear mitochondria (PNM, Figure 1C) were primarily located on opposite sides of the long axis of the nuclei.…”

Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function

“…However, compared with the IMF pool, SS mitochondria are more responsive to the effects of muscle use/disuse (2,3,27,36,47). Moreover, because of their close proximity to myonuclei (14,19), alterations in SS content and/or function that affect energy supply (40), reactive oxygen species production (55), and/or apoptotic stimuli (2, 3) may alter nuclear gene transcription in ways that modulate myofilament and/or mitochondrial function throughout the cell. This could occur through an effect of SS mitochondria to modulate myonuclear number, as animal models show that SS mitochondria produce more apoptotic stimuli in response to disuse (2), and it has been suggested that loss of myonuclei contributes to muscle atrophy (4).…”

Subcellular origin of mitochondrial DNA deletions in human skeletal muscle

“…Skeletal muscle fibers have a highly organized cytoarchitecture, where spatially-restricted mitochondrial subpopulations exist13, 14. Subsarcolemmal (SS) mitochondria are located at the periphery of the muscle fiber adjacent to the sarcolemma membrane, a subset of which are perinuclear intermyofibrillar (IMF) mitochondria are located between the myofibrils at the z-band.…”