The Pyruvate Dehydrogenase Complex Regulates Matrix Protein Phosphorylation and Mitophagic Selectivity

Panagiota Kolitsida,Vladimir Nolic,Jianwen Zhou,Michael Stumpe,Natalie M. Niemi,Jörn Dengjel,Hagai Abeliovich

bioRxiv（2023）

Dept. of Biochemistry | Department of Biology | Department of Biochemistry and Molecular Biophysics

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Abstract

The mitophagic degradation of mitochondrial matrix proteins in S. cerevisiae was previously shown to be selective, reflecting a pre-engulfment sorting step within the mitochondrial network. 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 understand the relationship between these two functions, we evaluated the role of the pyruvate dehydrogenase complex in mitophagic selectivity. Surprisingly, we identified a novel function of the complex in regulating mitophagic selectivity, which is independent of its enzymatic activity. Our data support a model in which the pyruvate dehydrogenase complex directly regulates the activity of its associated kinases and phosphatases. This regulatory interaction then determines the phosphorylation state of mitochondrial matrix proteins and their mitophagic fates.

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Cellular Self-Digestion

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