Figure 7.

The Proposed Working Model for PMI

(A) In healthy WT cells, a proportion of mitochondria will be destined for destruction due to age, damage, or dysfunction. Parkin-mediated ubiquitination (orange spheres) primes these mitochondria to enter the autophagic pathway and available P62 links them to LC3 (green spheres) and the growing autophagosome.

(B) In PMI-treated cells, P62 is more abundant therefore able to drive mitochondria into autophagy with increased efficiency.

(C) In cells where Parkin expression is reduced, a reduced number of mitochondria are primed for autophagy, so although P62 is overexpressed, the efficiency of mitophagy is reduced.

(D) Finally, in cells devoid of PINK1, Parkin is not recruited to mitochondria; however, redundant/alternative ubiquitin ligases may still be capable of ubiquitinating mitochondria, which can then be driven into autophagy by P62, albeit with reduced efficiency.