Lipid peroxidation products’ role in autophagy regulation

Autophagy, which is responsible for removing damaged molecules, prevents their accumulation in cells, thus maintaining intracellular homeostasis. It is also responsible for removing the effects of oxidative stress, so its activation takes place during increased reactive oxygen species (ROS) generation and lipid peroxidation. Therefore, the aim of this review was to summarize all the available knowledge about the effect of protein modifications by lipid peroxidation products on autophagy activation and the impact of this interaction on the functioning of cells. This review shows that reactive aldehydes (including 4-hydroxynonenal and malondialdehyde), either directly or by the formation of adducts with autophagic proteins, can activate or prevent autophagy, depending on their concentration. This effect relates not only to the initial stages of autophagy, when 4-hydroxynonenal and malondialdehyde affect the levels of proteins involved in autophagy initiation and phagophore formation, but also to the final stage, degradation, when reactive aldehydes, by binding to the active center of cathepsins, inactivate their proteolytic functions. Moreover, this review also shows how little research exists on analyzing the impact of lipid peroxidation products and their protein adducts on autophagy. Such knowledge could be used in the therapy of diseases related to autophagy disorders.