Abstract
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 same proteins also regulate the phosphorylation status and catalytic activity of the yeast pyruvate dehydrogenase complex, which is critical for mitochondrial metabolism. To better understand the relationship between these two functions, we evaluated the role of the pyruvate dehydrogenase complex in mitophagic selectivity. Interestingly, we identified a novel function of the complex in regulating mitophagy, which is independent of its enzymatic activity. Our data suggest an allosteric mechanism, wherein the pyruvate dehydrogenase complex directly regulates the activity of its cognate kinases and phosphatases to determine the phosphorylation state of mitochondrial matrix proteins and their mitophagic fate, in response to metabolic cues.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Updated Supplemental Table I
