BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium homeostasis to maintain skeletal muscle function

• Published in: iScience Vol. 27; no. 8; p. 110510
• Main Authors: Grepper, Dogan, Tabasso, Cassandra, Zanou, Nadège, Aguettaz, Axel K.F., Castro-Sepulveda, Mauricio, Ziegler, Dorian V., Lagarrigue, Sylviane, Arribat, Yoan, Martinotti, Adrien, Ebrahimi, Ammar, Daraspe, Jean, Fajas, Lluis, Amati, Francesca
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.08.2024; Elsevier
• Subjects: cell biology; pharmacology; cell biology; pharmacology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110510

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. [Display omitted] •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