Apoptosis represents a critical non-inflammatory mechanism for cell clearance in both physiological and pathological contexts, precisely regulated through the balance between pro-apoptotic and anti-apoptotic signaling. Three well-characterized apoptotic pathways have been identified: (1) the intrinsic (mitochondria-mediated) pathway, (2) the extrinsic (death receptor-mediated) pathway, and (3) the endoplasmic reticulum (ER)-stress pathway. These processes are coordinated through the mitochondria-associated endoplasmic reticulum membrane (MAMs), which serves as a vital coupling platform between mitochondria and the ER.MAMs play a pivotal role in maintaining Ca 2+ homeostasis and regulating apoptotic processes through several mechanisms. Dynamic alterations in MAMs architecture - including changes in gap width, contact number, and connection length - modulate apoptosis by influencing Ca 2+ trafficking and tethering protein expression. Key protein complexes localized at MAMs (including the IP3Rs-Grp75-VDAC1 complex, Mfn1/Mfn2 complex, and PTPIP51-containing complex) regulate apoptosis through three primary mechanisms: Ca 2+ homeostasis maintenance, lipid synthesis and transport, and mitochondrial morphology and dynamics. Furthermore, MAMs-mediated mitochondrial dynamics, particularly mitochondrial fission and cristae remodeling, contribute to apoptosis by facilitating Bax/Drp1 dimerization.This review systematically examines: how MAMs structural dynamics influence Ca 2+ signaling and tethering protein expression, the roles of MAMs-tethered proteins and their regulators in Ca 2+ homeostasis, lipid metabolism, and mitochondrial dynamics, and the impact of mitochondrial dynamics on Bax/Drp1 dimerization during apoptosis.