The fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis

Abstract

Although the mechanisms controlling skeletal muscle homeostasis have been identified, there is a lack of knowledge of the integrated dynamic processes occurring during myogenesis and their regulation. Here, metabolism, autophagy and differentiation were concomitantly analyzed in mouse muscle satellite cell (MSC)-derived myoblasts and their cross-talk addressed by drug and genetic manipulation. We show that increased mitochondrial biogenesis and activation of mammalian target of rapamycin complex 1 inactivation-independent basal autophagy characterize the conversion of myoblasts into myotubes. Notably, inhibition of autophagic flux halts cell fusion in the latest stages of differentiation and, conversely, when the fusion step of myocytes is impaired the biogenesis of autophagosomes is also impaired. By using myoblasts derived from p53 null mice, we show that in the absence of p53 glycolysis prevails and mitochondrial biogenesis is strongly impaired. P53 null myoblasts show defective terminal differentiation and attenuated basal autophagy when switched into differentiating culture conditions. In conclusion, we demonstrate that basal autophagy contributes to a correct execution of myogenesis and that physiological p53 activity is required for muscle homeostasis by regulating metabolism and by affecting autophagy and differentiation.

Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function

“…In addition to the action of taurine in oxidative stress, some research shows that taurine reduces the abundance of apoptotic signal proteins or rescues drug‐induced muscle atrophy . Regenerative processes are characterized by cellular cleansing (autophagy) and the formation of new muscle cells (myogenesis) . Little is known about the role of taurine in myogenesis and muscle regeneration.…”

Vacuolated PAS‐positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy

“…Similarly, we hypothesize that the occurrence of more than four PAS‐positive lymphocytes in the patient with dysfunction of G6PD, could be linked to altered autophagy regulation. Indeed, G6PD the rate‐limiting enzyme of the pentose phosphate pathway has been described to be an activator of autophagy (Dodson, Darley‐Usmar, & Zhang, ; Fortini et al, ; Zirin et al, ).…”

Nuclear co‐repressor (NCoR) is required to maintain insulin sensitivity in C2C12 myotubes

“…It is evident from the fact that NH 4 Cl, an inhibitor of lysosomal protein degradation pathway, increased NCoR protein level in the present study. Recently, two separate studies have reported onset of autophagy during differentiation of C 2 C 12 cells and mouse muscle satellite cell (MSC)‐derived myoblasts to promote mitochondrial biogenesis (Fortini et al, ; Sin et al, ). In fact, inhibition of autophagy distinctly interrupts with myogenesis in these studies.…”