Blink rates and disorders of movement

Summary The mitophagic degradation of mitochondrial matrix proteins is selective, reflecting a pre-engulfment sorting step. This selectivity is regulated through phosphorylation of mitochondrial matrix proteins by the matrix kinases Pkp1 and Pkp2, which in turn appear to be regulated by the phosphatase Aup1/Ptc6. However, these proteins also regulate the phosphorylation and catalytic activity of the yeast pyruvate dehydrogenase complex. To understand the relationship between these two functions, we tested the effect of deleting PDA1 on mitophagic selectivity. We report that pda1Δ cells show a mitophagy selectivity phenotype nearly identical to that of the pkp1Δ pkp2Δ double mutant. However, this is not due to a role for pyruvate dehydrogenase enzymatic activity in regulating mitophagy. Rather, our data suggest a novel mechanism wherein the pyruvate dehydrogenase complex directly regulates its cognate kinases and phosphatases, independent of its catalytic activity, to determine the phosphorylation state of mitochondrial matrix proteins in response to metabolic cues.