High‐Fat Diet Impairs Translocation of Phosphatidylserine From Mitochondria‐Associated Membranes ( MAM ) Into Mitochondria by the Conservative Mechanism From Fish to Tetrapod

signaling to mediate PS transfer, where dual grp75/mcu overexpression restores PS trafficking under lipotoxic stress; (3) MAM-dependent PS translocation is essential for maintaining mitochondrial dynamics and β-oxidation capacity, while its disruption under HFD promotes hepatic steatosis. Significantly, this study reveals that MAM-mediated PS homeostasis via the Ip3r-Grp75-Vdac/Mcu axis represents a conserved mechanism in tested species, offering new insights into vertebrate adaptations to lipid overload. These findings highlight MAMs as therapeutic targets for metabolic liver diseases through their role in linking PLs metabolism to mitochondrial function.