Fig. 3: The regulations of BNIP3L and mitophagic activity.
From: BNIP3L/NIX-mediated mitophagy: molecular mechanisms and implications for human disease
A Regulation of BNIP3L in the nucleus. BNIP3L is transcriptionally upregulated by several transcriptional factors, including hypoxia-inducible factor-1alpha (HIF1A), TP53, and FOXO3. In addition, DNA methylation ensures epigenetic regulation of BNIP3L. B Regulation of BNIP3L by micro RNAs (e.g., miR-347, miR-30, miR-302/367, and miR-133a). C The role played by BNIP3L in modulating autophagy. BNIP3L disrupts the BCL2-BECN1 complex; the released BECN1 subsequently promotes the formation of autophagosomes. Additionally, BNIP3L inhibits MTORC1 by prohibiting RHEB activity and subsequently induces autophagy. We note that the interaction between BNIP3L and RHEB can be enhanced by the accumulation of cardiolipin. D The role played by BNIP3L as a mitophagy receptor. The BNIP3L LIR motif interacts with LC3s to induce mitophagy. The BNIP3L monomer fails to induce mitophagy. BNIP3L phosphorylation at different sites regulates mitophagic activity but the associated kinases and phosphatases have not yet been identified. E BNIP3L dimer is required for mitophagy and is prone to degradation by the proteasome. PARK2 ubiquitinates BNIP3L and promotes mitophagy. Additional E3 ligases participating in BNIP3L degradation have not yet been identified.
