Dietary Vitamin K2 Isoforms Restore Redox Balance, Organelle Integrity, and Genomic Stability under Streptozotocin-Induced Oxidative Stress in Differentiated SH-SY5Y Cells

Abstract Among the two dietary vitamin K2 isoforms, MK-4 is abundantly found in the brain, and MK-7 is well absorbed and has a longer half-life. Beyond canonical functions, these dietary vitamin K2 vitamers have emerged as bioactive nutrients with potential cytoprotective properties. However, their presence in the brain and their functional relevance in modulating oxidative-stress-associated organelle damage, genomic instability, and neurite integrity remain insufficiently characterized. Streptozotocin led to impaired cellular bioenergetics, followed by organelle damage and genotoxicity. Post-treatment with MK-4 and MK-7 significantly attenuated ROS accumulation, enhanced antioxidant capacity, and preserved mitochondrial functional integrity, as evidenced by improved mitochondrial footprint, reduced mitochondrial ROS, restored ATP levels, and regulated mitophagy. Furthermore, vitamin K2 isoforms mitigated endoplasmic reticulum/Golgi stress, significantly reduced DNA damage, and improved neurite growth. Thus, vitamin K2 isoforms function as multifunctional dietary bioactive compounds with potential relevance for maintaining cell homeostasis during oxidative-stress-associated neuronal dysfunction.