SFXN2 contributes mitochondrial dysfunction‑induced apoptosis as a substrate of Parkin

Mitochondrial proteins and mitochondrial functions are interdependent. In this study, we confirm that the protein level of SFXN2 decreases significantly during mitochondrial damage, primarily due to proteasome-mediated degradation. Parkin, a mitochondrial E3 ligase, facilitates the polyubiquitination and proteasomal degradation of SFXN2. Reduced SFXN2 exacerbates mitochondrial damage‑induced cell death across multiple cell lines, while elevated expression of SFXN2 protects neurons from the mitochondrial stress. Taken together, this work identifies SFXN2, as a Parkin substrate, that mitigates mitochondrial damage and possesses anti‑apoptosis effect, and its reduction contributes to mitochondrial damage‑induced cell death in various cell lines, including 293T, SH‑SY5Y, and N2a cells. RNA-seq profiling of wildtype HEK293 cells(NC_HA) and their stable overexpressing of SFXN2(OE_HA).