Fig. 9

The levels of miR-27a/b are increased under chronic mitophagic flux condition. a, b HeLa cells were incubated with DMSO, 10 μM CCCP, or combination of 10 μM oligomycin and 4 μM antimycin as indicated. miR-27a/b levels were measured by qRT-PCR and normalized to corresponding U6 levels. Data are shown as fold changes relative to the DMSO controls. Values are mean ± SEM (t-test, **p < 0.01, ***p < 0.001). c A proposed role of miR-27a/b in mitophagy. Upon chronic mitophagic flux, the levels of miR-27a/b are increased and miR-27a/b function as a negative feedback loop to turn off excessive mitophagic flux. Upon the induction of miR-27a/b expression, the translation of PINK1 mRNA is inhibited by miR-27a/b. Consequently, the level of PINK1 protein in mitochondria decreases and thereby, autophagic degradation of the damaged mitochondria by lysosome is inhibited (Left panel). In contrast, PINK1 translation and lysosomal clearance of damaged mitochondria are increased when PINK1 inhibition mediated by miR-27a/b was disinhibited by the low levels of miR-27a/b (Right panel)