AUTHOR=Varma Sudhir R. , Ani Omar H. A. A. , Narayanan Jayaraj K. , Mathew Asok TITLE=The role of Mitofusin-1 and Mitofusin-2 in periodontal disease: a comprehensive review JOURNAL=Frontiers in Oral Health VOLUME=Volume 6 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oral-health/articles/10.3389/froh.2025.1540178 DOI=10.3389/froh.2025.1540178 ISSN=2673-4842 ABSTRACT=Periodontal disease is a widespread chronic inflammatory state influencing the supporting anatomy of the teeth, distinguished by oxidative stress, progressive bone loss, and tissue damage. Recent articles have highlighted the significance of mitochondrial dynamics, mainly Mitofusin-1 (MFN1) along with Mitofusin-2 (MFN2), inflammation regulation, tissue homeostasis, and in cellular function. The aim of the current study is to comprehensively review including evaluate the roles of MFN2 and MFN1 in the pathogenesis as well as the progression of periodontal disease, foregrounding their effect on mitochondrial integrity, inflammatory pathways, and oxidative stress. Studies were selected depending on inclusion criteria based on the roles of MFN2 and MFN1 in periodontal disease and health. Data from chosen in vivo, clinical studies, and in vitro were synthesized. Outcomes indicate that MFN2 and MFN1 are important for preserving cellular function, mitigating oxidative damage, and mitochondrial fusion. Decreased levels of these proteins were related to elevated oxidative stress, inflammation, and increased mitochondrial dysfunction in periodontal tissues. The current comprehensive review shows the important roles of MFN1 along with MFN2 in inflammation regulation, cell survival, and mitochondrial dynamics within periodontal disease. The prospective for targeting MFN1 along with MFN2 in therapeutic policy is promising, presenting avenues for upgraded periodontal management and regeneration.