Résumé
The physical connection between mitochondria and endoplasmic reticulum (ER) is an essential signaling hub to ensure organelle and cellular functions. In skeletal muscle, ER-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. In adult zebrafish, we found that the loss of Bcl2l13 impairs skeletal muscle structure and function. Ca2+ signaling is altered in Bcl2l13 knockout animals and mitochondrial complexes activity is decreased. Organelle fractioning in mammalian cells shows BCL2L13 at mitochondria, ER, and mitochondria-associated membranes. ER-mitochondria contact sites number is not modified by BCL2L13 modulation, but knockdown of BCL2L13 in C2C12 cells changes cytosolic Ca2+ release and mitochondrial Ca2+ uptake. This suggests that BCL2L13 interaction with mitochondria and ER, and its role in Ca2+ signaling, contributes to proper skeletal muscle function.
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•Loss of Bcl2l13 negatively affects swimming capacity and skeletal muscle integrity•Bcl2l13 loss alters mitochondrial function and morphology•BCL2L13 localizes to ER-mitochondria contact sites•Bcl2l13 KD increases mitochondrial Ca2+ uptake and regulates Ca2+ dynamics
Pharmacology; Cell biology