Ablation of Acid Ceramidase Impairs Autophagy and Mitochondria Activity in Melanoma Cells

Cutaneous melanoma is often resistant to therapy due to its high plasticity, as well as its ability to metabolise chemotherapeutic drugs. Sphingolipid signalling plays a pivotal role in its progression and metastasis. One of the ways melanoma alters sphingolipid rheostat is via over-expression of lysosomal acid ceramidase (AC), which catalyses the hydrolysis of pro-apoptotic long-chain ceramides into sphingosine and fatty acid. In this report, we examine the role of acid ceramidase in maintaining cellular homeostasis through the regulation of autophagy and mitochondrial activity in melanoma cell lines. We show that under baseline conditions, wild-type melanoma cells had 3-fold higher levels of the autophagy marker, microtubule-associated proteins 1A/1B light chain 3B (LC3 II), compared to AC-null cells. This difference was further magnified after cell starvation. Moreover, we noticed autophagy impairment in A375 AC-null cells, possibly due to local accumulation of non-metabolized ceramides. Nonetheless, we observed that AC-null cells exhibited a significant increase in mitochondrial membrane potential compared to control cells. Consistent with this observation, we found that, after total starvation, ~30% of AC-null cells undergo apoptosis compared to ~6% of wild-type cells. As expected, AC transfection restored viability in A375 AC-null cells. Together, these findings suggest that AC-null melanoma cells change and adapt their metabolism to survive in the absence of AC, although in a way that does not allow them to cope with the stress of nutrient deprivation.

Survival and Recovery of the Pine-Tree Lappet Dendrolimus pini When Subjected to Simulated Starvation

There are many reasons to study the survival and recovery of animals after starvation in simulated transport conditions or other passive dispersal methods. To do so, we chose Dendrolimus pini, an economically important pest of Scots pine with great potential in terms of passive dispersal outside its territory. In this work, we sought to answer the following questions: What is the maximum survival of different instar larvae after total starvation? Does access to dry tissues of the preferred host plant extend the lifespan of the larvae? Does the possibility of larvae recovery exist after starvation for various periods? We found that older larvae survived longer without food than younger larvae. Moreover, dry food did not extend the lifespan of the larvae. Our observations showed that insects were interested in food and tasted it at the beginning, but they did not feed on it for long. Furthermore, larvae recovery was indeed possible, and the time of starvation did not significantly affect this. We generally concluded that the D. pini larvae were characterized by the ability to survive without food for up to one month, which confirms that this species is able to survive long durations of transport to almost anywhere in the world.

Modeling of lipid and protein depletion during total starvation

This study presents a model describing lipid and protein depletion of an individual facing total starvation. The model distinguishes two compartments of body mass: a metabolic compartment and a structural compartment. It is considered that the lipids and the proteins of the metabolic compartment ensure the totality of physiological functions. The main assumptions of the model lie in the definitions of lipid mass and protein mass of the metabolic compartment, which are related to total lipid mass and total body mass, respectively. Under these assumptions, for a given individual, the ratio of lipid and protein utilization rates is proportional to the adiposity. The model accounts for the protein sparing observed at high adiposity levels and enables us to discuss the individual's survival in relation to the levels of lipid and protein depletion. The time course of changes in lipid and protein depletion rates can be calculated by introducing the energy expenditure of the individual. In simulations, it was assumed that specific energy expenditure was constant during starvation and that mortality occurred at a critical level of protein depletion. The most characteristic results derived from these simulations concern the kinetics of protein depletion, which depend markedly on initial adiposity. Accordingly, in obese subjects, the rate of protein losses remains fairly constant during fasting, whereas it increases from the onset of the fast in lean subjects, in agreement with experimental observations. In the model, protein and lipid depletion rates are both proportional to energy expenditure, which needs to be confirmed from complementary data.