Fig. 7: Schematic working model shows the oncogenic role of SFXN2 in alleviating mitochondrion autophagy while enhancing energy production and HO1-mediated anti-oxidative effect in MM cells.

The upper panel shows that SFXN2 is involved in mitochondrial heme biosynthesis for ATP production as well as the by-product ROS generation. Cytosol iron acquired from TFR1 is either stored in FTH1 or released as labile iron pool (LIP). Then it is exported by a mitochondrial heme exporter FVLCR1b identified in erythrocytes to transfer into mitochondria by MFRN1/2 for mitochondrial ATP synthesis during ETC couples with TCA and OXPHOS. SFXN2 regulates mitochondrial iron utilization and anti-oxidative stress together with HO1. The lower panel indicates that SFXN2 promotes MM cell proliferation through maintaining the homeostasis among mitochondrial bioenergetics, autophagy, iron metabolism, and redox in an interconnected way. Color or bold letters present molecules/processes in this study, and gray letters indicate molecules/processes in other research work. Solid arrows mean direct interaction, and dashed lines or arrows mean indirect effects.