Autophagy: a necessary defense against extreme cadmium intoxication in a multigenerational 2D experiment

Abstract

Autophagy is a natural process that aims to eliminate malfunctioning cell parts, organelles or molecules under physiological conditions. It is also induced in response to infection, starvation or oxidative stress to provide energy in case of an energy deficit. The aim of this 2-dimensional study was to test if, and if so, how, this process depends on the concentration of cadmium in food (with Cd concentrations from 0 to 352 μg of Cd per g of food (dry weight)—D1 dimension) and the history of selection pressure (160 vs 20 generations of exposure to Cd—D2 dimension). For the study, the 5th instar larvae of a unique strain of the moth Spodoptera exigua that was selected for cadmium tolerance for 160 generations (44 μg of Cd per g of food (dry weight)), as well as 20-generation (11, 22 and 44 μg of Cd per g of food (dry weight)) and control strains, were used. Autophagy intensity was measured by means of flow cytometry and compared with life history parameters: survivability and duration of the 3rd larval stage. The highest values of autophagy markers were found in the groups exposed to the highest Cd concentration and corresponded (with a significant correlation coefficient) to an increased development duration or decreased survivorship in the respective groups. In conclusion, autophagy is probably initiated only if any other defense mechanisms, e.g., antioxidative mechanisms, are not efficient. Moreover, in individuals from pre-exposed populations, the intensity of autophagy is lower.

Exploring the Connection between Autophagy and Heat-Stress Tolerance in Drosophila melanogaster

“…Overall, autophagy's role in protecting from abiotic stressors such a desiccation, toxics, or direct oxidative damages in ectotherms has been highlighted numerous times (Moore et al, 2006, Bjedov et al, 2009Minois et al, 2012;Teets and Denlinger, 2013;Mizunoe et al, 2018;Zhang et al, 2019;Babczyńska et al, 2020, Valko et al, 2021. In the specific case of thermal stress, further correlations between autophagy genes upregulation and cold acclimation have been made (Gerken et al, 2015;Des Marteaux et al, 2017;Tachibana et al, 2019).…”

“…In response to stress, or exposure to rapamycin, inhibition of TOR has been linked to the upregulation of autophagy and downregulation of the synthesis of proteins that are not involved in the stress response, at the expense of cellular proliferation (Wullschleger et al, 2006). This contributes to the maintain of proteostasis, and autophagy has repeatedly been linked with enhanced tolerance to starvation, desiccation, heavy metals, toxic and oxidative damages in a variety of organisms, including insects (Moore et a., 2006;Bjedov et al, 2009, Minois et al, 2012Teets and Denlinger, 2013;Mizunoe et al, 2018;Zhang et al, 2019;Babczyńska et al, 2020, Valko et al, 2021. In the specific case of heat-stress, it has been demonstrated that activation of HSF-1 induces autophagy in multiple tissues in the ectothermic nematode Caenorhabditis elegans, which reduces protein denaturation and increases survival (Kumsta et al, 2017).…”

“…This both directly mitigates the potential damages caused by abiotic stress while improving cellular metabolic robustness and survival by maximizing ATP and metabolite availability [36]. Modulation of autophagy, that relate to a more global responses from the TOR pathway, has therefore ultimately linked to enhanced survival to various stressors in animals, including insects, such as starvation, desiccation, toxics, heavy metals or oxidative damage [22,23,[37][38][39][40][41][42][43]. In the specific case of heat-stress, it has been demonstrated that activation of the transcription factor HSF-1 which controls the cellular heat-shock response, and transcription of heatinducible Hsps, also induces autophagy in multiple tissues in Caenorhabditis elegans [14].…”

A review of transgenerational and multigenerational toxicology in the in vivo model animal Caenorhabditis elegans

“…Autophagy, a process of cellular self‐destruction in response to stress, starvation or infection, was usually related to apoptosis. But existing research only detected low intensity autophagy during multigenerational exposure (Babczynska et al, 2020; Dziewiecka et al, 2020), and the role of autophagy in multigenerational effects still need further study. In addition, due to the limitation in available evidence, it is largely unclear whether different pollutants including metals, organics, and particulate pollutants share the exact cellular mechanisms during controlling transgenerational toxicity.…”

Exploring the connection between autophagy and heat-stress tolerance in Drosophila melanogaster

“…TOR inhibition can thus both directly mitigate the potential damages caused by abiotic stress through autophagy induction, while also improving cellular metabolic robustness and survival by maximizing ATP and metabolite availability at the expense of cellular proliferation and organismal growth [38,43]. Accordingly, increased survival upon exposure to various stressors such as starvation, desiccation, toxins, oxidative damage, and cold exposure has been correlated with modulation of autophagy in ectotherms [21,22,41,[44][45][46][47][48][49][50][51][52][53]. In the specific case of heat-stress, it has been demonstrated that activation of the transcription factor HSF-1, which controls the cellular heat-shock response and transcription of heat-inducible Hsps, also induces autophagy in multiple tissues in Caenorhabditis elegans [13].…”