Ceramide alters mitochondrial dynamics and reduces mitochondrial respiration in skeletal muscle

Abstract

Fat gain is associated with ceramide accrual in tissues of high‐metabolic rate, such as liver, brain and skeletal muscle. We predict that ceramide accumulation in skeletal muscle affects mitochondrial morphology and physiology. We found that ceramide treatment on murine myoblasts decreased viable mitochondrial density and induced mitochondrial fission, possibly via dynamin‐related protein 1 (Drp1), which was increased with ceramide accrual. Inhibition of endogenous ceramide synthesis via myriocin and serine palmitoyltransferase 2 (SPT2) siRNA prevented fatty acid‐induced mitochondrial fission in myoblasts. Moreover, inhibition of ceramide biosynthesis prevented the reduction in mitochondrial O2 consumption in myoblasts treated with fatty acids. Altogether, these findings suggest a critical role for ceramide in altering mitochondrial dynamics and function. Ongoing work will determine the extent to which mitochondrial fission mediates the adverse alterations in mitochondrial function. This work was supported by a BYU Graduate Research Fellowship (MES) and a BYU Mentoring Environment Grant (BTB).