Figure 1.

Model for SCF-FBXL4 function in mitophagy suppression. The SCF-FBXL4 ubiquitin ligase localizes to the mitochondrial outer membrane and mediates the constitutive ubiquitination and subsequent proteasomal degradation of BNIP3L and BNIP3 mitophagy receptors, thereby preventing excessive mitophagy. Loss of FBXL4 results in the stabilization and upregulation of these receptors, which ultimately leads to increased mitophagy. Pathogenic variants in FBXL4 associated with MTDPS13 are unable to effectively downregulate BNIP3L and BNIP3, leading to their accumulation and consequent elevated mitophagy. Figure was created with BioRender.