NIPSNAP3A regulates cellular homeostasis by modulating mitochondrial dynamics

[Display omitted] •NIPSNAP3A knockdown reduces cell proliferation and migration in HeLa cells.•Knockdown of NIPSNAP3A reduced Actinomycin D-induced apoptosis by decreasing the release of Cytochrome C.•Knocking down NIPSNAP3A decreased the phosphorylation of Drp1 at Ser616, inhibiting mitochondrial fission. Mitochondria are essential for cell metabolism and survival as they produce the majority of cellular ATP through oxidative phosphorylation as well as regulate critical processes such as cell proliferation and apoptosis. NIPSNAP family of proteins are predominantly mitochondrial matrix proteins. However, the molecular and cellular functions of the NIPSNAPs, particularly NIPSNAP3A, have remained elusive. Here, we demonstrated that NIPSNAP3A knockdown in HeLa cells inhibited their proliferation and migration and attenuated apoptosis induced by Actinomycin D (Act-D). These findings suggested a complex relationship between cellular processes and mitochondrial functions, mediated by NIPSNAP3A. Further investigations revealed that NIPSNAP3A knockdown not only inhibited mitochondrial fission through reduction of DRP1-S616, but also suppressed cytochrome c release in apoptosis. Collectively, our findings highlight the critical role of NIPSNAP3A in coordinating cellular processes, likely through its influence on mitochondrial dynamics.