Fig. 3

Mitophagy pathways by Uro-A activates are represented schematically. By maintaining the kinase PINK1 in a stable state, Uro-A triggers PINK1-Parkin-mediated mitophagy (red arrow). Parkin is subsequently brought into PINK1 and ubiquitinates the proteins in the mitochondria. The build-up of phosphorylated mitochondrial proteins results from PINK1’s subsequent phosphorylation of ubiquitin chains. By raising mitochondrial BNIP3 (BCL2 Interacting Protein 3) levels, Uro-A activates a PINK1—Parkin-independent pathway (blue arrow). Independently of Parkin and other docking proteins, BNIP3 recruits LC3 (Microtubule-associated protein 1A/1B-light chain 3). It permits the development of a phagosome membrane around the mitochondria for both mitophagy routes. Lysosomes and the originating mitophagosome combine. Low pH and lysosomal hydrolytic enzymes ultimately lead to the demise of the mitochondria. This illustration was created with Biorender.com