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. Overall design: RNA-seq profiling of wildtype HEK293 cells(NC_HA) and their stable overexpressing of SFXN2(OE_HA).