Regulation of mitochondrial biogenesis during myogenesis

Abstract

Pathways involved in mitochondrial biogenesis associated with myogenic differentiation are poorly defined. Therefore, C 2 C 12 myoblasts were differentiated into multinucleated myotubes and parameters/regulators of mitochondrial biogenesis were investigated.Mitochondrial respiration, citrate synthase-and β-hydroxyacyl-CoA dehydrogenase activity as well as protein content of complexes I, II, III and V of the mitochondrial respiratory chain increased 4-8 fold during differentiation. Additionally, an increase in the ratio of myosin heavy chain (MyHC) slow vs MyHC fast protein content was observed. PPAR transcriptional activity and transcript levels of PPAR-α, the PPAR co-activator PGC-1α, mitochondrial transcription factor A and nuclear respiratory factor 1 increased during differentiation while expression levels of PPAR-γ decreased. In conclusion, expression and activity levels of genes known for their regulatory role in skeletal muscle oxidative capabilities parallel increases in oxidative parameters during the myogenic program. In particular, PGC-1α and PPAR-α may be involved in the regulation of mitochondrial biogenesis during myogenesis.

Nuclear Recruitment of Neuronal Nitric-oxide Synthase by α-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis

“…6, A and B), together with an enhancement of mitochondrial mass (Fig. 6B), was detected in differentiating myocytes, with an extent comparable to that reported in the literature (48). Interestingly, nNOS content did not change in total extracts (Fig.…”

Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype

“…Indeed, muscle reloading has been shown to be associated with muscle regeneration, which involves myogenesis (19,37,43). Moreover, we and others have convincingly shown, not only that myogenesis and muscle regeneration are associated with a potent induction of mitochondrial biogenesis and activation of PGC-1-coactivated signaling events (32,47), but also that myogenesis and myogenesis-induced activation of oxidative metabolism are highly interdependent processes (18,34). Although a causal involvement of activated alternative NF-B signaling in reloading-induced activation of muscle OXPHEN cannot be concluded from our experiment, our data and the recently identified role of the alternative NF-B pathway in the control of muscle OXPHEN (5) and the observation that alternative NF-B activation is potently induced during myogenesis (6) in concert with myogenesis-induced OXPHEN development strongly suggest a role for the alternative NF-B signaling pathway in reloading-induced activation of muscle OXPHEN.…”

Skeletal Muscle Stem Cells: Effects of Aging and Metabolism on Muscle Regenerative Function

“…This is particularly true in skeletal muscle, where the stem cell turnover rate is extremely low, even in comparison to other adult stem cells (Remels et al 2010). The lack of satellite cells entering cell cycle, together with their inevitable exposure to oxidative and inflammatory stress (a by-product of normal metabolism and local muscle injury), makes aged satellite cells particularly vulnerable to the accumulation of cellular and genotoxic insults, which can cause irreversible damage to key cellular macromolecules, such as proteins, lipids, and nucleic acids.…”