Hoan Van Ngo, Stevens Robertin, Dominik Brokatzky, Magdalena K. Bielecka, Damián Lobato‐Márquez, Vincenzo Torraca and Serge Mostowy 2023. Septins promote caspase activity and coordinate mitochondrial apoptosis. Cytoskeleton. 80 (7/8), pp. 254-265. https://doi.org/10.1002/cm.21696
| Title | Septins promote caspase activity and coordinate mitochondrial apoptosis |
|---|---|
| Type | Journal article |
| Authors | Hoan Van Ngo, Stevens Robertin, Dominik Brokatzky, Magdalena K. Bielecka, Damián Lobato‐Márquez, Vincenzo Torraca and Serge Mostowy |
| Abstract | Apoptosis is a form of regulated cell death essential for tissue homeostasis and embryonic development. Apoptosis also plays a key role during bacterial infection, yet some intracellular bacterial pathogens (such as Shigella flexneri, whose lipopolysaccharide can block apoptosis) can manipulate cell death programs as an important survival strategy. Septins are a component of the cytoskeleton essential for mitochondrial dynamics and host defense, however, the role of septins in regulated cell death is mostly unknown. Here, we discover that septins promote mitochondrial (i.e., intrinsic) apoptosis in response to treatment with staurosporine (a pan-kinase inhibitor) or etoposide (a DNA topoisomerase inhibitor). Consistent with a role for septins in mitochondrial dynamics, septins promote the release of mitochondrial protein cytochrome c in apoptotic cells and are required for the proteolytic activation of caspase-3, caspase-7, and caspase-9 (core components of the apoptotic machinery). Apoptosis of HeLa cells induced in response to infection by S. flexneri ΔgalU (a lipopolysaccharide mutant unable to block apoptosis) is also septin-dependent. In vivo, zebrafish larvae are significantly more susceptible to infection with S. flexneri ΔgalU (as compared to infection with wildtype S. flexneri), yet septin deficient larvae are equally susceptible to infection with S. flexneri ΔgalU and wildtype S. flexneri. These data provide a new molecular framework to understand the complexity of mitochondrial apoptosis and its ability to combat bacterial infection. |
| Journal | Cytoskeleton |
| Journal citation | 80 (7/8), pp. 254-265 |
| ISSN | 1949-3592 |
| Year | 2023 |
| Publisher | Wiley |
| Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1002/cm.21696 |
| Web address (URL) | https://doi.org/10.1002/cm.21696 |
| Publication dates | |
| Published online | 23 Apr 2022 |
| Published in print | Jul 2023 |