Alteration of mitochondrial function in the livers of mice with glycogen branching enzyme deficiency.

Glycogen storage disease type IV (GSD IV) is caused by mutations in the glycogen branching enzyme gene (GBE1) that lead to the accumulation of aberrant glycogen in affected tissues, mostly in the liver. To determine whether dysfunctional glycogen metabolism in GSD IV affects other components of cellular bioenergetics, we studied mitochondrial function in heterozygous Gbe1 knockout (Gbe1+/-) mice. Mitochondria isolated from the livers of Gbe1+/- mice showed elevated respiratory complex I activity and increased reactive oxygen species production, particularly by respiratory chain complex III. These observations indicate that GBE1 deficiency leads to broader rearrangements in energy metabolism and that the mechanisms underlying GSD IV pathogenesis may include more than merely mechanical cell damage caused by the presence of glycogen aggregates.

Changes in mitochondrial reactive oxygen species synthesis during differentiation of skeletal muscle cells.

Myogenesis is accompanied by an intensive metabolic remodeling. We investigated the mitochondrial reactive oxygen species (ROS) generation at different levels of skeletal muscle differentiation: in C2C12 myoblasts, in C2C12 myotubes and in adult mouse skeletal muscle. Differentiation was accompanied by an increase in mitochondrial content and respiratory chain activity. The detected ROS production levels correlated with mitochondrial content, being the lowest in the myoblasts. Unlike the adult skeletal muscle, myoblast ROS production was significantly stimulated by the complex I inhibitor rotenone. Our results show that mitochondria are an important ROS source in skeletal muscle cells. The substantial changes in mitochondrial ROS synthesis during skeletal muscle differentiation can be explained by intensive bioenergetic remodeling.

[Glycogenoses--genetic disorders leading to disturbed glycogen metabolism]. / Glikogenozy--choroby genetyczne zwiazane z zaburzeniami metabolizmu glikogenu.

Glycogen storage diseases (GSD, glycogenoses) is a group of genetic disorders resulting from abnormal metabolism of glycogen--a polymeric molecule involved in intercellular glucose storage. Currently 13 different types of glycogenoses are known. They all result from mutations in genes for different enzymes, which directly or indirectly regulate glycogen synthesis and degradation. The clinical manifestation of GSDs encompasses primarily liver, striated muscle and brain tissue dysfunction. In those tissues glycogen plays a particularly important role. spectrum and severity of symptoms is very diverse, depending on both the type and subtype of the disease as well as on the individual features of the patient. The therapy is based mainly on application of an appropriate diet. Enzyme replacement therapy is currently available for GSD type II. For some of the other types the possibility for gene therapy is intensively investigated.