Pptc7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy.

Autor:	Niemi NM; Morgridge Institute for Research, Madison, WI, 53715, USA.; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA., Serrano LR; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Muehlbauer LK; Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Balnis C; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Kozul KL; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia., Rashan EH; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Shishkova E; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA., Schueler KL; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Keller MP; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Attie AD; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA., Pagan J; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia.; The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia., Coon JJ; Morgridge Institute for Research, Madison, WI, 53715, USA.; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA., Pagliarini DJ; Morgridge Institute for Research, Madison, WI, 53715, USA.; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 01. Date of Electronic Publication: 2023 Mar 01.
DOI:	10.1101/2023.02.28.530351
Abstrakt:	Pptc7 is a resident mitochondrial phosphatase essential for maintaining proper mitochondrial content and function. Newborn mice lacking Pptc7 exhibit aberrant mitochondrial protein phosphorylation, suffer from a range of metabolic defects, and fail to survive beyond one day after birth. Using an inducible knockout model, we reveal that loss of Pptc7 in adult mice causes marked reduction in mitochondrial mass concomitant with elevation of the mitophagy receptors Bnip3 and Nix. Consistently, Pptc7 -/- mouse embryonic fibroblasts (MEFs) exhibit a major increase in mitophagy that is reversed upon deletion of these receptors. Our phosphoproteomics analyses reveal a common set of elevated phosphosites between perinatal tissues, adult liver, and MEFs-including multiple sites on Bnip3 and Nix. These data suggest that Pptc7 deletion causes mitochondrial dysfunction via dysregulation of several metabolic pathways and that Pptc7 may directly regulate mitophagy receptor function or stability. Overall, our work reveals a significant role for Pptc7 in the mitophagic response and furthers the growing notion that management of mitochondrial protein phosphorylation is essential for ensuring proper organelle content and function. Competing Interests: Conflict of interest The following conflicts of interest have been declared: J.J.C. is a consultant for Thermo Fisher Scientific, 908 Devices, and Seer.
Databáze:	MEDLINE
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