Autophagy and Metabolism

Abstract

Autophagy is a process of self-cannibalization. Cells capture their own cytoplasm and organelles and consume them in lysosomes. The resulting breakdown products are inputs to cellular metabolism, through which they are used to generate energy and to build new proteins and membranes. Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however-cancer cells exploit it to survive in nutrient-poor tumors.Living organisms from yeast to humans are capable of eating parts of themselves in order to survive. This involves the degradation of cellular components, either because they are deleterious (e.g., damaged organelles and microbial invaders) or because the resulting breakdown products are needed to support metabolism. This process was aptly termed autophagy from the Greek "auto" or oneself and "phagy" or to eat. It has gained attention recently as an essential contributor to human health and disease.There are several forms of autophagy, each of which involves delivering intracellular cargo to lysosomes for degradation. The predominant form, macroautophagy (autophagy hereafter), produces vesicles called autophagosomes that capture and deliver cytoplasmic material to lysosomes (1). The autophagy-related genes (the atg genes) are conserved from yeast to mammals and regulate the cannibalism of intracellular cytoplasm, proteins, and organelles.Autophagy is the only mechanism to degrade large structures such as organelles and protein aggregates. In the absence of stress, basal autophagy serves a housekeeping function. It provides a routine "garbage disposal" service to cells, eliminating damaged components that could otherwise become toxic. Such cellular refreshing is particularly important in quiescent and terminally differentiated cells, where damaged components are not diluted by cell replication. In starvation, autophagy provides a nutrient source, promoting survival. Autophagy is induced by a broad range of other stressors and can degrade protein aggregates, oxidized lipids, damaged organelles, and even intracellular pathogens. Although it is not always possible to resolve the metabolic and garbage disposal roles for autophagy, it is clear that autophagy prevents disease. Defects in autophagy are linked to liver disease, neurodegeneration, Crohn's disease, aging, cancer, and metabolic syndrome.

FTO levels affect RNA modification and the transcriptome

“…Recently, several links between body weight regulation and autophagy in the liver, adipose tissue and hypothalamic cells have been established. [24][25][26] Although we were not able to verify reduced transcripts levels of the ATG5 gene by qRT-PCR, the possible link between autophagy and FTO function may merit further examination. In view of the link between autophagy and ciliary function (see eg, Huber et al 27 ), it is worth noting that overexpression and depletion of FTO affected transcript levels of several genes involved in ciliary function (indicated by * in Supplementary Tables S1 and S3).…”

Autophagy and ageing: Insights from invertebrate model organisms

“…Upon completion of autophagosome formation, the Atg12-Atg5-Atg16 complex is released into the cytosol, whereas Atg8-PE stably associates with the autophagosomal membranes. This highly specific association has facilitated assays that exploit Atg8 localization to autophagosomes as a proxy to monitor autophagy in vivo (Chen and Klionsky, 2011;Rabinowitz and White, 2010). Lysosome docking and fusion occurs when the outer autophagosomal membrane fuses with the lysosomal membrane producing an autolysosome (an autophagic body in yeast).…”

La mort cellulaire programmée ne manque pas de vocabulaire

“…Dans ce type de mort, la chromatine n'est pas condensée, le cytoplasme présente une vacuolisation très importante et les cellules ne sont pas ou peu reconnues par des phagocytes. Pour détecter l'autophagie, différentes techniques sont utilisées comme la visualisation des autophagosomes par microscopie électronique, la redistribution de LC3 au niveau des membranes d'autophagosomes ou encore l'apparition de sa forme dérivée (LC3-II) qui se distingue de la forme non modifiée (LC3-I) par une analyse sur gel de polyacrylamide [20]. L'invalidation génétique de plusieurs gènes de la famille Atg a démontré leur implication dans la régulation de cette voie.…”