Mitochondrial fission mediates ceramide-induced metabolic disruption in skeletal muscle

Ceramide is a sphingolipid that serves as an important second messenger in an increasing number of stress-induced pathways. Ceramide has long been known to affect the mitochondria, resulting in altered mitochondrial physiology. We sought to assess the impact of ceramide on skeletal muscle mitochondrial structure and function. A primary observation was the dramatic division of mitochondria in ceramide-treated cells. This effect is likely a result of increased Drp1 action, as ceramide increased Drp1 expression and Drp1 inhibition prevented mitochondrial fission despite ceramide. Further, we found that ceramide treatment reduced mitochondrial O2 consumption (i.e., respiration) in cultured myotubes and permeabilized red gastrocnemius muscle fiber bundles. Ceramide treatment also increased H2O2 levels and reduced Akt/PKB phosphorylation in myotubes. However, inhibition of mitochondrial fission via Drp1 blockade completely protected the myotubes and fiber bundles from ceramide-induced metabolic disruption, including maintained mitochondrial respiration, reduced H2O2 levels, and unaffected insulin signaling. These data suggest that the forced and sustained mitochondrial fission that results from ceramide accrual may alter metabolic function in skeletal muscle, which is a prominent site not only of energy demand (via the mitochondria), but also of ceramide accrual with weight gain.

Source: BJ Cell - September 30, 2013 Category: Biochemistry Authors: M E. Smith, T S. Tippetts, E S. Brassfield, B J. Tucker, A Ockey, A C. Swensen, T S. Anthonymuthu, T D. Washburn, D A. Kane, J T. Prince, B T. Bikman Tags: BJ Metabolism Source Type: research