BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium homeostasis to maintain skeletal muscle function
Dogan Grepper 1, Cassandra Tabasso 1, Nadège Zanou 2, Axel K F Aguettaz 1 3, Mauricio Castro-Sepulveda 1, Dorian V Ziegler 4, Sylviane Lagarrigue 1, Yoan Arribat 1, Adrien Martinotti 1 3, Ammar Ebrahimi 1 3, Jean Daraspe 5, Lluis Fajas 4, Francesca Amati 1 3
. 2024 Jul 14;27(8):110510.
- PMID: 39175772
- PMCID: PMC11340602
- DOI: 10.1016/j.isci.2024.110510
Abstract
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.