Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis

Abstract

During apoptosis, cells undergo characteristic morphological changes in which the cytoskeleton plays an active role. The cytoskeleton rearrangements have been mainly attributed to actinomyosin ring contraction, while microtubule and intermediate filaments are depolymerized at early stages of apoptosis. However, recent results have shown that microtubules are reorganized during the execution phase of apoptosis forming an apoptotic microtubule network (AMN). Evidence suggests that AMN is required to maintain plasma membrane integrity and cell morphology during the execution phase of apoptosis. The new “two coffins” hypothesis proposes that both AMN and apoptotic cells can adopt two morphological patterns, round or irregular, which result from different cytoskeleton kinetic reorganization during the execution phase of apoptosis induced by genotoxic agents. In addition, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses. These findings suggest that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response. From a pathological point of view, round-shaped apoptosis can be seen as a physiological and controlled type of apoptosis, while irregular-shaped apoptosis can be considered as a pathological type of cell death closer to necrosis.

The activation of antioxidant and apoptosis pathways involved in damage of human proximal tubule epithelial cells by PM2.5 exposure

“…Cell apoptosis, also known as programmed cell death, is a highly autonomic process that involves biochemical reactions and changes in cell characteristics [47]. Changes in early apoptotic morphology include cell shrinkage, cell membrane blebbing and chromosome concentration, and late apoptosis is characterized by the formation of apoptotic bodies and DNA fragmentation [48,49]. Similarly, we observed that a part of PM 2.5 -treated cells displayed apoptotic morphological changes in their nuclei, including formation of chromatin condensation and apoptotic bodies ( Fig.…”

Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis

“…Such discrepancies might occur due to different molecular mechanisms of collagen production and formation of α‐SMA–positive fibers, even though both features usually appear together in emerging fibrosis. Neither type I collagen nor α‐SMA are direct predicted targets of miR‐125b; therefore, we assume that reduced formation of α‐SMA–positive fibers may be a result of cytoskeleton reorganization due to cells entering a proapoptotic status , which is discussed below. Thus, while previously identified differentially expressed miRs in SSc promote fibrosis, in this study we demonstrated a novel role of microRNAs in the pathophysiology of SSc: the down‐regulation of miR‐125b in SSc exerts protective counterregulatory effects on the progression of skin fibrosis.…”

Redox‐Mediated Transient Reconfiguration of a Supramolecular Assembly

“…Self‐(re)organization, i. e. spatiotemporal ordering is a common phenomenon observed in nature . Cytoskeletal elements, organelles and cells undergo reorganization into different sizes, shapes and composition during the phases of cell division and this reconfiguration facilitates the various functional processes . Nature accomplishes this spatiotemporal control by dissipative self‐assembly .…”