Presenilin 1 is located in the mitochondrial inner inner membrane and regulates mitochondrial cristae junction protein arrangement and cristae formation in HEK293 cells

leads to abnormal mitochondrial cristae structure. Further analysis reveals that PS1 interacts with mitochondrial inner membrane proteins. Its absence promotes ATAD3A oligomerization and disrupts its arrangement at mitochondrial cristae junctions, leading to expansion of the mitochondria-associated membrane and instability of mitochondrial DNA. Our findings demonstrate that PS1 acts as a central regulator of mitochondrial cristae morphogenesis by modulating protein interaction networks at cristae junctions, thereby illuminating fundamental molecular mechanisms contributing to mitochondrial dysfunction in Alzheimer's disease.