Structural functionality of skeletal muscle mitochondria and its correlation with metabolic diseases

Abstract

The skeletal muscle is one of the largest organs in the mammalian body. Its remarkable ability to swiftly shift its substrate selection allows other organs like the brain to choose their preferred substrate first. Healthy skeletal muscle has a high level of metabolic flexibility, which is reduced in several metabolic diseases, including obesity and Type 2 diabetes (T2D). Skeletal muscle health is highly dependent on optimally functioning mitochondria that exist in a highly integrated network with the sarcoplasmic reticulum and sarcolemma. The three major mitochondrial processes: biogenesis, dynamics, and mitophagy, taken together, determine the quality of the mitochondrial network in the muscle. Since muscle health is primarily dependent on mitochondrial status, the mitochondrial processes are very tightly regulated in the skeletal muscle via transcription factors like peroxisome proliferator-activated receptor-γ coactivator-1α, peroxisome proliferator-activated receptors, estrogen-related receptors, nuclear respiratory factor, and Transcription factor A, mitochondrial. Physiological stimuli that enhance muscle energy expenditure, like cold and exercise, also promote a healthy mitochondrial phenotype and muscle health. In contrast, conditions like metabolic disorders, muscle dystrophies, and aging impair the mitochondrial phenotype, which is associated with poor muscle health. Further, exercise training is known to improve muscle health in aged individuals or during the early stages of metabolic disorders. This might suggest that conditions enhancing mitochondrial health can promote muscle health. Therefore, in this review, we take a critical overview of current knowledge about skeletal muscle mitochondria and the regulation of their quality. Also, we have discussed the molecular derailments that happen during various pathophysiological conditions and whether it is an effect or a cause.

Characterization of differential distribution patterns between mitofusin isoforms and their interaction in developing skeletal muscles of rat

“…Interestingly, mitochondrial distribution at individual fiber levels showed a striking difference between adult and neonate muscles. While in adult fibers SDH activity is found in the peripheral region (these most likely are subsarcolemmal mitochondria [SSM]), 25 in neonatal fibers, SDH activity is uniformly distributed throughout the CSA (Figure 2C). SSM occupies a large area of adult muscle fibers: 56.26% of the total fiber area in the gastrocnemius and 45.96% in the quadriceps.…”

Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle

“…One could hypothesize that TLR4-induced inflammation could immobilize mitochondria, but this must be investigated and confirmed in future studies. Calcium release from the endoplasmic reticulum and shuttle to mitochondria could contribute to the regulation of mitochondrial cristae by TLR4 ( Swalsingh et al, 2022 ). In summary, our results show that LPS induced a mitochondrial fragmented phenotype and induced alterations in mitochondrial cristae, which was reversed upon LPS co-treatment with TAK 242 in human myotubes.…”

Mitochondrial Quantity and Quality in Age-Related Sarcopenia

“…Skeletal muscle accounts for about 40% of total body mass in mammals and is essential for balance, posture, and locomotion [1]. This organ also holds remarkable metabolic properties and adaptability to metabolic needs [2] with a role as an endocrine signaling system [3]. Alterations in muscle metabolic plasticity and signaling have been described in the setting of conditions associated with age (e.g., sarcopenia) and muscle atrophy (e.g., disuse).…”