PPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy

• DOI: 10.1038/s41467-023-42069-w
• Publication Date: 2023-10-13T09:01:35Z
• Authors: Natalie M. Niemi; Lia R. Serrano; Laura K. Muehlbauer; Catherine E. Balnis; Lianjie Wei; Andrew J. Smith; Keri-Lyn Kozul; Merima Forny; Olivia M. Connor; Edrees H. Rashan; Evgenia Shishkova; Kathryn L. Schueler; Mark P. Keller; Alan D. Attie; Jonathan R. Friedman; Julia K. Pagan; Joshua J. Coon; David J. Pagliarini
• Keywords: Knockout mouse

Abstract PPTC7 is a resident mitochondrial phosphatase essential for maintaining proper content and function. Newborn mice lacking Pptc7 exhibit aberrant protein phosphorylation, suffer from range of metabolic defects, fail to survive beyond one day after birth. Using an inducible knockout model, we reveal that loss in adult causes marked reduction mass capacity with elevated hepatic triglyceride accumulation. animals increased expression the mitophagy receptors BNIP3 NIX, -/- mouse embryonic fibroblasts (MEFs) display major increase reversed upon deletion these receptors. Our phosphoproteomics analyses common set phosphosites between perinatal tissues, liver, MEFs, including multiple sites on our molecular studies demonstrate can directly interact dephosphorylate proteins. These data suggest dysfunction via dysregulation several pathways may regulate receptor function or stability. Overall, work reveals significant role mitophagic response furthers growing notion management phosphorylation ensuring organelle