Autophagy and apoptosis in planarians

Abstract

Adult planarians are capable of undergoing regeneration and body remodelling in order to adapt to physical damage or extreme environmental conditions. Moreover, most planarians can tolerate long periods of starvation and during this time, they shrink from an adult size to, and sometimes beyond, the initial size at hatching. Indeed, these properties have made them a classic model to study stem cells and regeneration. Under such stressful conditions, food reserves from the gastrodermis and parenchyma are first used up and later the testes, copulatory organs and ovaries are digested. More surprisingly, when food is again made available to shrunken individuals, they grow back to adult size and all their reproductive structures reappear. These cycles of growth and shrinkage may occur over long periods without any apparent impairment to the individual, or to its future maturation and breeding capacities. This plasticity resides in a mesoderm tissue known as the parenchyma, which is formed by several differentiated non-proliferating cell types and only one mitotically active cell type, the neoblasts, which represent approximately 20-30% of the cells in the parenchyma. Neoblasts are generally thought to be somatic stem-cells that participate in the normal continuous turnover of all cell types in planarians. Hence, planarians are organisms that continuously adapt their bodies (morphallaxis) to different environmental stresses (i.e.: injury or starvation). This adaptation involves a variety of processes including proliferation, differentiation, apoptosis and autophagy, all of which are perfectly orchestrated and tightly regulated to remodel or restore the body pattern. While neoblast biology and body re-patterning are currently the subject of intense research, apoptosis and autophagy remain much less studied. In this review we will summarize our current understanding and hypotheses regarding where and when apoptosis and autophagy occur and fulfil an essential role in planarians.

Bioelectric signaling regulates head and organ size during planarian regeneration

“…We next sought to elucidate the mechanism by which H,K-ATPase ion transport activity regulates organ size and proportion. The scaling of existing tissues to maintain body proportion during regeneration in planarians appears to involve apoptotic tissue remodeling (Pellettieri and Sanchez Alvarado, 2007;Gonzalez-Estevez and Salo, 2010;Pellettieri et al, 2010;Bender et al, 2012), including the caspase family of regulators (Hwang et al, 2004;Gonzalez-Estevez et al, 2007). Apoptosis in planarians undergoes two peaks (inversely localized to the mitotic peaks); the first apoptotic peak (from 1 to 4 hpa) is at the wound site, whereas the second peak (at 3 dpa) is dispersed throughout the animal (Pellettieri et al, 2010).…”

Thapsigargin induces apoptosis when autophagy is inhibited in HepG2 cells and both processes are regulated by ROS-dependent pathway

“…Autophagy is an intracellular contained event which does not necessarily mean cellular destruction, whilst apoptosis is ordered cellular destruction. Recent studies show that the molecular regulators of both pathways are interconnected and the same regulators can sometimes control both apoptosis and autophagy (González-Estévez and Saló, 2010;Yousefi et al, 2006). Multiple stress signals, such as reactive oxygen species (ROS) and ER Stress can mediate the process of both autophagy and apoptosis in several types of cancer cells.…”

Expression of hsp90 mediates cytoprotective effects in the gastrodermis of planarians

“…In addition to their extraordinary stem cell-based regenerative capacity, planarians are incredibly resistant to prolonged starvation during which they become markedly reduced in size, again growing back to the normal size after regular feeding (Bowen et al 1976). A variety of perfectly orchestrated proliferative and cell death programs are responsible of this extraordinary body plasticity, contributing to adapt planarians to stress conditions (González-Estévez et al 2007a, b;González-Estévez and Saló 2010;Pellettieri et al 2010). A major surviving strategy to long periods of nutrient deprivation is activation of self-eating, autophagic processes that lead to the breakdown of nonvital components and the release of nutrients, ensuring vital functions for the whole organism.…”

“…A major surviving strategy to long periods of nutrient deprivation is activation of self-eating, autophagic processes that lead to the breakdown of nonvital components and the release of nutrients, ensuring vital functions for the whole organism. Authophagy is particularly important in nondividing cells (Mizushima et al 2008), and, in planarians, food reserves from the gastrodermis and parenchyma cells are first recruited to tolerate long periods of starvation (González-Estévez 2008;González-Estévez and Saló 2010). A tightly regulated induction of HSPs also constitutes an important cell defense mechanism to protect these organisms from the effects of deleterious stress conditions.…”