Figure 8.

Autophagic potential influences adaptability to stress. Autophagy pathway is active in all eukaryotic cells at a basal rate, which contributes to the maintenance of cellular homeostasis. This basal autophagic activity can be further increased in response to intracellular or extracellular stimuli, including distinct forms of stress at the cell, tissue or organism level.¹ In wild-type mice, autophagy mitigates the detrimental effects of stress, from cellular to organismal level. Contrarily, a total autophagy impairment (as it is the case in mutant mice lacking Atg3, Atg5 or Atg7) impacts cellular homeostasis, especially in non-proliferating cells, which progressively accumulate cellular damage in the absence of autophagy.⁴⁵ Eventually, these defects impact tissue-specific functions although the precise consequences and severity of autophagy impairment are variable among different tissues.¹¹ At the organismal level, a total loss of autophagy leads to perinatal death.^{2, 10} Interestingly, a partial reduction of autophagic potential as that in Atg4b-deficient mice does not compromise organism viability, although leads to tissue-specific alterations^{20, 46} and reduced resilience upon stressful conditions. Finally, the pharmacological stimulation of autophagy (by the treatment with spermidine, for example) increases basal levels of the process, which improves tissue fitness and leads to a reduced sensitivity to environmental stressors, including high-fat diet