Asymmetrical disassembly of apoptotic cells and the mechanisms underpinning this process

Jiang L, Tixeira R, Atkin-Smith G, Caruso S, Phan K, Baxter A, Hulett M and Poon I

La Trobe Institute for Molecular Science, La Trobe University.

Apoptotic bodies (ApoBD) generated from apoptotic cells is considered a major class of extracellular vesicles that could facilitate cell clearance and intercellular communication. Efficient disassembly and clearance of dying cells is significant in avoiding accumulation of cellular debris, also the release of pro-inflammatory intracellular contents. Thus, the disassembly of apoptotic cells may also play a key role in preventing autoimmune diseases such as systemic lupus erythematosus. However, the mechanisms underpinning this process is not entirely clear yet. When observing T cells undergoing apoptosis by time-lapse microscopy, we discovered the establishment of asymmetric form “octopus structure” during apoptosis. Moreover, by using fluorescent microscope, we discovered that cellular organelle (e.g. nucleus, mitochondria, Golgi apparatus and lysosomes) and cell surface markers are also distributed asymmetrically as well during apoptotic membrane blebbing, which will then lead to asymmetrical disassembly and the generation of distinct apoptotic bodies with different contents and morphological characteristics. Additionally, we discovered similar morphology in different cell lines during apoptosis, indicating a unified cellular content sorting mechanism during apoptotic cell disassembly. Furthermore, we found that dynamic blebbing is essential for asymmetrical distribution of nuclear content and ROCK1 inhibitor GSK can inhibit this process efficiently. Overall, these data uncover a novel characteristic of apoptotic cell disassembly and molecular regulators involved in this process.