Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3.

ABSTRACT: Mitofusin 1 (MFN1) plays a crucial role in mitochondrial fusion and oocyte development. However, its function in preimplantation embryonic development and its potential involvement in epigenetic regulation remain poorly understood. In this study, it is shown that MFN1 interacts with PADI6, a key component of the cytoplasmic lattice in oocytes and early embryos. MFN1 deficiency in mice results in reduced PADI6 levels and decreased expression of translational machinery components, which suppress protein synthesis activity and lower histone H3.3 abundance. These disruptions lead to the failure of male pronucleus formation, aberrant zygotic genome activation, and impaired embryonic development. It is further demonstrated that the MFN1 activator S89 promotes H3.3 incorporation and rescues early

SUBMITTER: Shi XY 

PROVIDER: S-EPMC12079336 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature