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

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.

SUBMITTER: Grepper D 

PROVIDER: S-EPMC11340602 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature