Raising Ca ²⁺ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle

Abstract

ABSTRACT Skeletal muscle adapts to endurance exercise with an increase in mitochondria. Muscle contractions generate numerous potential signals. To determine which of these stimulates mitochondrial biogenesis, we are using L6 myotubes. Using this model we have found that raising cytosolic Ca 2+ induces an increase in mitochondria. In this study, we tested the hypothesis that raising cytosolic Ca 2+ in L6 myotubes induces increased expression of PGC‐1, NRF‐1, NRF‐2, and mtTFA, factors that have been implicated in mitochondrial biogenesis and in the adaptation of muscle to exercise. Raising cytosolic Ca 2+ by exposing L6 myotubes to caffeine for 5 h induced significant increases in PGC‐1 and mtTFA protein expression and in NRF‐1 and NRF‐2 binding to DNA. These adaptations were prevented by dantrolene, which blocks Ca 2+ release from the SR. Exposure of L6 myotubes to caffeine for 5 h per day for 5 days induced significant increases in mitochondrial marker enzyme proteins. Our results show that the adaptive response of L6 myotubes to an increase in cytosolic Ca 2+ mimics the stimulation of mitochondrial biogenesis by exercise. They support the hypothesis that an increase in cytosolic Ca 2+ is one of the signals that mediate increased mitochondrial biogenesis in muscle.

Keywords

Affiliated Institutions

• Washington University in St. Louis US

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