Abstract

Autophagy is an evolutionary conserved cellular self-degradation process considered as a major energy mobilizing system in eukaryotes. It has long been considered as a post-translationally regulated event, and the importance of transcriptional regulation of autophagy-related genes (atg) for somatic maintenance and homeostasis during long period of stress emerged only recently. In this regard, large changes in atg transcription have been documented in several species under diverse types of prolonged catabolic situations. However, the available data primarily concern atg mRNA levels at specific times and fail to capture the dynamic relationship between transcript production over time and integrated phenotypes. Here, we present the development of a statistical model describing the dynamics of expression of several atg and lysosomal genes in European glass eel (Anguilla anguilla) during long-term fasting at two temperatures (9 °C and 12 °C) and make use of this model to infer the effect of transcripts dynamics on an integrated phenotype – here weight loss. Our analysis shows long-term non-random fluctuating atg expression dynamics and reveals for the first time a significant contribution of atg transcripts production over time to weight loss. The proposed approach thus offers a new perspective on the long-term transcriptional control of autophagy and its physiological role.

Highlights

  • IntroductionArrivals of European glass eels Anguilla anguilla dramatically dropped (by up to 90%), leading to an important decline in continental stocks of eels[1]

  • Over the last decades, arrivals of European glass eels Anguilla anguilla dramatically dropped, leading to an important decline in continental stocks of eels[1]

  • Since glass eels were sampled at different fasting duration, any non-random pattern in the temporal dynamics of gene expression of the whole population can inform on the temporal dynamics of each individual profile

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Summary

Introduction

Arrivals of European glass eels Anguilla anguilla dramatically dropped (by up to 90%), leading to an important decline in continental stocks of eels[1]. The species life cycle spans over a large area and through various ecosystems from the Sargasso Sea, where spawning occurs, to the European continental shelf, where larvae undergo a first metamorphosis into glass eel[2] At this stage, glass eels display a large panel of migratory tactics, ranging from residency in marine water, to various degrees of upstream colonization through estuarine and freshwater ecosystems[3]. The level of autophagy increases during prolonged periods of cellular stress in many eukaryotic species (from yeast to mammals) in order to conserve energy and promote survival In this context, and because glass eels undergo strong fasting while colonizing continental ecosystems, genetic- and environment-related variations of autophagy function can strongly affect their migratory ability as well as their sex and their subsequent survival. With depletion of available ATG, the demand is accomplished by synthesizing new proteins through transcription and translation to maintain cellular homeostasis[9]

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