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. 2021 Dec 22;65(7):913–923. doi: 10.1042/EBC20210036

Figure 2. PINK1/Parkin-mediated mitophagy.

Figure 2

(1) In depolarised mitochondria, PINK1 associates with the OMM through TOM, but its import through TIM is inhibited. (2) Full-length PINK1 is then activated on the OMM through dimerisation and autophosphorylation of Serine 228 and 402. (3) PINK1 then phosphorylates several targets, including ubiquitin (Ub) that is present on various OMM proteins through the action of MARCH5. (4) Phospho-ubiquitin allows the binding of Parkin, which is also phosphorylated and activated by PINK1. (5) Activated Parkin further ubiquitinates a range of OMM proteins, which can act as (6, inset) further substrates for PINK1 and subsequent binding of Parkin, resulting in a strong positive-feedback loop. (7) Phospho-ubiquitin allows the binding of the autophagy receptors Optineurin and NDP52 and the subsequent formation of the autophagosomal membrane through the binding of LC3.