Mitochondrial fission and remodelling contributes to muscle atrophy.

Mitochondria are crucial organelles in the production of energy and in the control of signalling cascades. A machinery of pro-fusion and fission proteins regulates their morphology and subcellular localization. In muscle this results in an orderly pattern of intermyofibrillar and subsarcolemmal mitochondria.

FoxO3 controls autophagy in skeletal muscle in vivo.

Autophagy allows cell survival during starvation through the bulk degradation of proteins and organelles by lysosomal enzymes. However, the mechanisms responsible for the induction and regulation of the autophagy program are poorly understood. Here we show that the FoxO3 transcription factor, which plays a critical role in muscle atrophy, is necessary and sufficient for the induction of autophagy in skeletal muscle in vivo.

Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics.

The transcription factors myogenin and MyoD have been suggested to be involved in maintaining slow and fast muscle-fiber phenotypes, respectively, in rodents. Whether this is also the case in human muscle is unknown. To test this, 4 wk of chronic, low-frequency electrical stimulation training of the tibialis anterior muscle of paraplegic subjects were used to evoke a fast-to-slow transformation in muscle phenotype.

Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy.

Skeletal muscle atrophy is a debilitating response to fasting, disuse, cancer, and other systemic diseases. In atrophying muscles, the ubiquitin ligase, atrogin-1 (MAFbx), is dramatically induced, and this response is necessary for rapid atrophy. Here, we show that in cultured myotubes undergoing atrophy, the activity of the PI3K/AKT pathway decreases, leading to activation of Foxo transcription factors and atrogin-1 induction.

Topology of Homer 1c and Homer 1a in C2C12 myotubes and transgenic skeletal muscle fibers.

mRNA transcripts for Homer 1a and Homer 1c have been detected in skeletal muscle [Biochem. Biophys. Res.

Heart morphogenesis is not affected by overexpression of the Sh3bgr gene mapping to the Down syndrome heart critical region.

Congenital heart disease (CHD) is the most common birth defect in humans and is present in 40% of newborns affected by Down syndrome (DS). The SH3BGR gene maps to the DS-CHD region and is a potential candidate for the pathogenesis of CHD, since it is selectively expressed in cardiac and skeletal muscle. To determine whether overexpression of Sh3bgr in the murine heart may cause abnormal cardiac development, we have generated transgenic mice using a cardiac- and skeletal-muscle-specific promoter to drive the expression of a Sh3bgr transgene.

Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation.

We have characterized a novel unconventional myosin heavy chain, named MYO18B, that appears to be expressed mainly in human cardiac and skeletal muscles and, at lower levels, in testis. MYO18B transcript is detected in all types of striated muscles but at much lower levels compared to class II sarcomeric myosins, and it is up regulated after in vitro differentiation of myoblasts into myotubes. Phylogenetic analysis shows that this myosin belongs to the recently identified class XVIII, however, unlike the other member of this class, it seems to be unique to Vertebrate since it contains two large amino acid domains of unknown function at the N and C-termini.

Training by low-frequency stimulation of tibialis anterior in spinal cord-injured men.

The tibialis anterior muscle of nine paraplegic men was chronically stimulated (2-6 h per day; at 10 Hz, 5 s on, 5 s off) under isometric loading conditions for 5 days per week for 4 weeks. After 4 weeks of training, muscle fatigue resistance in an electrically evoked test had increased by an average of 75% (P <.01, n = 9), but there were no changes in the relative composition of the three myosin heavy chain (MHC) isoforms.