Chaperone-assisted selective autophagy (CASA) is a tension-induced degradation pathway essential for muscle maintenance. Impairment of CASA causes childhood muscle dystrophy and cardiomyopathy. However, the importance of CASA for muscle function in healthy individuals has remained elusive so far. Here we describe the impact of strength training on CASA in a group of healthy and moderately trained men. We show that strenuous resistance exercise causes an acute induction of CASA in affected muscles to degrade mechanically damaged cytoskeleton proteins. Moreover, repeated resistance exercise during 4 wk of training led to an increased expression of CASA components. In human skeletal muscle, CASA apparently acts as a central adaptation mechanism that responds to acute physical exercise and to repeated mechanical stimulation.

Calcium (Ca²⁺) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca²⁺ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca²⁺ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca²⁺-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca²⁺ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca²⁺ ions in adult muscle but also highlight recent findings of critical Ca²⁺-dependent mechanisms essential for skeletal muscle-regulation and maintenance.

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Satellite cells (SCs) are the resident stem cells of skeletal muscle tissue which play a major role in muscle adaptation, e.g. as a response to physical training. The aim of this study was to examine the effects of an intermittent lactate (La) treatment on the proliferation and differentiation of C2C12 myoblasts, simulating a microcycle of high intensity endurance training. Furthermore, the involvement of reactive oxygen species (ROS) in this context was examined. C2C12 myoblasts were therefore repeatedly incubated for 2 h each day with 10 mM or 20 mM La differentiation medium (DM) and in some cases 20 mM La DM plus different antioxidative substances for up to 5 days. La free (0 mM) DM served as a control. Immunocytochemical staining, Western blot analysis and colorimetric assays were used to assess oxidative stress, proliferation, and differentiation. Results show that La induces oxidative stress, enhances cell-cycle withdrawal, and initiates early differentiation but delays late differentiation in a timely and dose-dependent manner. These effects can be reversed by the addition of antioxidants to the La DM. We therefore conclude that La has a regulatory role in C2C12 myogenesis via a ROS-sensitive mechanism which elicits implications for reassessing some aspects of training and the use of nutritional supplements.

Skeletal muscle is responsible for altered acute and chronic workload as induced by exercise. Skeletal muscle adaptations range from immediate change of contractility to structural adaptation to adjust the demanded performance capacities. These processes are regulated by mechanically and metabolically induced signaling pathways, which are more or less involved in all of these regulations. Nitric oxide is one of the central signaling molecules involved in functional and structural adaption in different cell types. It is mainly produced by nitric oxide synthases (NOS) and by non-enzymatic pathways also in skeletal muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is underlined by the differential subcellular expression of NOS1, NOS2, and NOS3, and the alteration of NO production provoked by changes of workload. In skeletal muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity and proper signaling mechanisms during adaptation processes towards mechanical and metabolic stimulations are taken over by NO signaling. The NO signaling can be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation-dependent modulation of effector molecules involved in contractile and metabolic adaptation to exercise. In this review, we describe the most recent findings of NO signaling in skeletal muscle with a special emphasis on exercise conditions. However, to gain a more detailed understanding of the complex role of NO signaling for functional adaptation of skeletal muscle (during exercise), additional sophisticated studies are needed to provide deeper insights into NO-mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle physiology.