Ferroptosis is a distinct form of cell death that is driven by iron-dependent phospholipid peroxidation. Polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA) and adrenal acid (AdA), are most prone to lipid peroxidation, which induces ferroptosis and affects the function of cell membranes. In this study, we discovered that AA induces ferritinophagy in hepatocytes, a selective form of autophagy that degrades ferritin, triggering unstable iron overload. Mechanistically, AA enhances cellular uptake of bound iron by up-regulating transferrin receptor 1 (TfR1). Additionally, AA induces endoplasmic reticulum stress (ER stress) and simultaneously activates two of its branches, pancreatic ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1). Notably, PERK and IRE1 appear to play distinct roles in inducing ferritinophagy. Inhibition of PERK reduced the AA-induced increase of Fe2+ by alleviating ferritinophagy, while inhibition of IRE1 further exacerbated ferroptosis by activating ferritinophagy. Furthermore, there seems to be an interaction between the signaling pathways of ER stress, and inhibition of IRE1 exacerbates AA-induced ferritinophagy by further activating the PERK signaling pathway, thereby exacerbating the extent of cell death. Collectively, our findings suggest that iron overload is involved in AA-induced hepatocyte ferroptosis and that this process is regulated by ER stress-mediated ferritinophagy. This study suggests potential therapeutic strategies for treating liver diseases related to lipid metabolism disorders by intervening in the ferroptosis process.

Prepared aquatic products refer to ready-to-eat, heated, ready-to-cook, and paired food derived from marine products, which are growing as attractive convenience food. Flavor is a vital factor for consumers in choosing prepared aquatic products. Suitable packaging materials and methods are the crucial pathways used to maintain the flavor and control the off-flavor of prepared aquatic products. Compared to vacuum packaging and modified atmosphere packaging, innovative packaging, including biodegradable, edible, active, and intelligent packaging, has received attention due to the potential advantages of flavor regulation. The mechanism of flavor change in package-associated prepared aquatic products is surveyed in this paper according to the reaction of lipids, proteins, microorganisms, and enzymes. Further, the effects of innovative packaging materials and methods on the flavor regulation of prepared aquatic products are summarized under the investigation of typical packaging. Moreover, prospects for innovative packaging materials and methods for flavor regulation in prepared aquatic products are proposed. This review provides references and bases for developing innovative packaging that maintain the flavor and wipes off-flavor.