BCL2L13 regulates sarcoplasmic reticulum-mitochondria calcium flux in skeletal muscle

The physical connection between mitochondria and endoplasmic or sarcoplasmic reticulum is an essential signaling hub to ensure organelle and cellular functions. In skeletal muscle, ER/SR-mitochondria calcium (Ca2+) signaling is crucial to maintain cellular homeostasis during physical activity. High expression of BCL2L13, a member of the BCL-2 family, was suggested as an adaptive response in endurance-trained human subjects. The aim of this study was to describe the molecular and physiological functions of BCL2L13. Using a zebrafish knockout model, we assessed the physiological changes, alterations of skeletal muscle structure, differences in the muscle proteome, and mitochondrial metabolism caused by the loss of Bcl2l13. We used cellular models to define the subcellular location and the mechanistic role of Bcl2l13. The loss of Bcl2l13 in zebrafish decreased swimming capacity and activity. Skeletal muscle fast fiber cross sectional area was reduced in knockout fish. Muscle proteome uncovered changes in protein turnover, transmembrane transport and expression of Ca2+ signaling proteins compared to wild type fish.