Nesprin-2 Giant translocates from the nuclear envelope to mitochondria during apoptosis
2Department of Pathology and Cell Biology, Physicians and Surgeons, Columbia University, USA
3Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, USA
Nesprin-2 Giant (herein nesprin-2G) is the largest isoform of the nesprin-2 protein family, and is a part of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, connecting the nucleus to the cytoskeleton. We recently found that under apoptotic stress, the pro-apoptotic protein Bax has a non-canonical function, promoting the generation and rupture of nuclear bubbles (termed SIGRUNB), resulting in nuclear proteins redistribution (NPR) to the cytoplasm. We also found that Bax and nesprin-2G can interact and that this interaction increases during apoptosis. We now find that nesprin-2G is present around nuclear bubbles. However, it is not crucial for the apoptotic-induced effect of Bax on NPR, since knocking out Nesprin-2G in mouse embryonic fibroblasts does not affect NPR or SIGRUNB. We also show that during apoptosis, around the time of mitochondrial dysfunction, nesprin-2G translocates from the nuclear envelope to the mitochondria. This suggests a pro-apoptotic role of nesprin-2G in mitochondria, possibly linked to its interaction with Bax.