MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v03/MSV000085796/primary200OK0000Marcus Kruegerhttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=10c0dd3938ff419884f5daff6237ef94marcus.krueger@uni-koeln.deMassIVE81MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetProteomicsQ Exactive HFMus Musculus (ncbitaxon:10090)CECAD Research Center, Institute for Genetics, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 CologneHeart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein kinase 2. Ablation of Perm1 in mice results in reduced protein expression of lipin-1 accompanied by accumulation of specific phospholipid species. Isolation of Perm1-deficient mitochondria revealed significant downregulation of mitochondrial transport proteins for amino acids and carnitines, including SLC25A12/13/29/34 and CPT2. Consistently, we observed altered levels of various lipid species, amino acids, and acylcarnitines in Perm1^-/- mitochondria. We conclude that the outer mitochondrial membrane protein PERM1 regulates homeostasis of lipid and amino acid metabolites in mitochondria.Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.Aravamudhan Sriram S, Türk Clara C, Bock Theresa T, Keufgens Lena L, Nolte Hendrik H, Lang Franziska F, Krishnan Ramesh Kumar RK, König Tim T, Hammerschmidt Philipp P, Schindler Natalie N, Brodesser Susanne S, Rozsivalova Dieu Hien DH, Rugarli Elena E, Trifunovic Aleksandra A, Brüning Jens J, Langer Thomas T, Braun Thomas T, Krüger Marcus Mblack death, Plantaris, outer mitochondrial membrane, Herz, REC1L, Anterior, methionine aminopeptidase activity, determination, Laboratory, phospholipids, FON1, Skeletal, Inner, postnatal development, Mus domesticus, Aminosaeure, Anterior Tibial Muscle, Uros1, Amino acid, CAT-1, adult heart, growth and development, CASP-14, protein, FLORAL ORGAN NUMBER 1, Mitochondrial Contractions, House Mouse, phosphorylation, prevention, BB129864, circulatory vessel, protein polypeptide chains, Mitochondrial Membranes, A830037N07Rik, PGC-1v, SUP, 2, Kinase, protein aggregate, Fs(3)Hor, prevention and control, peptidase M activity, mitochondrion outer membrane, adenomas, rabGAPLP, L-methionine aminopeptidase activity, DmelCG2684, Muscle Tissues, amino acids, malignant fibrohistiocytic tumours, reference sample, heart or heart like organ, Gm11133, dERR, Tissue, AI839531, Bdr, CG7404, T25658, hypoplasia, RabGAP-5, Swiss Mice, proteins, purification, NTef2, cardiac structure, Super protein, inhibition of homeostatic process, sp, infection by Yersinia pestis, SNAP-25, 2610002D09Rik, preventive measures, isolation and purification, Muscles, Inner Mitochondrial Membrane, PBGD, RUSC3, homeostasis, 2610009E16Rik, cardiac morphogenesis, ATP Phosphotransferases, Ppargc1, outer mitochondrion membrane, Gastrocnemius, AI323697, ATP, dorsal tube, vertebrate heart, preventive therapy, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma/high-grade spindle cell sarcoma, Aminokarbonsaeure, MYH-associated polyposis, mouse, autosomal recessive familial adenomatous polyposis, Maps, Mitochondrial Protein, Phosphatides, results, alpha-amino carboxylic acids, Fs(3)Sz11, Pgc1, chambered heart, positive regulation of homeostatic process, Voluntary Muscle, Solute carrier family 7 member 1, Voluntary, Mini-ICE, Inner Mitochondrial Membranes, Lipid, Voluntary Muscles, GENA70, simple tissue, cardium, ATRC1, regulator, autosomal recessive, ARALAR, ParaT, Mus musculus, Amino Acid, Acid, RUTBC3, Transphosphorylases, Mitochondrial, ENSMUSG00000079510, Caspase-14 subunit p10, Amino acids, Outer, mice, cardiac myocyte proliferation, Swiss Mouse, heart muscle cell proliferation, malignant fibrohistiocytic tumors, Caspase-14 subunit p19, MICE, early, muscle element, RABGAP5, domesticus, Carnitine palmitoyltransferase 2 deficiency, DmelCG7404, AGC1, Horka, multiple colorectal, CG2684, Fs(3)Horka, 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retroviral leukemia receptor, Anterior Tibial, Controlled, striated muscle, small, Autoregulation, Controlling, MUTYH-Associated Polyposis, protein complex, Carnitine palmitoyltransferase II (CPT II) deficiency, CPTASE, Proteins, Phosphorylations, HCAT1, CPT1, Hearts, alpha-amino acids, Synaptosomal-associated 25 kDa protein, Mitochondrial., Muscle, motif, cardiac development, Phosphotransferases, Lipin-1, Pgc-1alpha, development, Soleus, Contractions, somatic muscle, 3.1.3.4, native protein, natural protein, Mus, Protein, chemical analysis, heart, regulation of homeostatic process, Membranes, a phospholipid derivative, Soleus Muscle, underdeveloped, Kinases, prophylaxis, postnatal growth, House Mice, FLO10, muscle, MYH-Associated Polyposis, Membrane, Amino, Lds, HERP, Laboratory Mice, Protein Gene Products, Outer Mitochondrial Membrane, Mitochondrial Contraction, Gene Proteins, mitochondria, activation of homeostatic process, control, SNAP, Inner Mitochondrial, dorsal vessel development, 2310042D19Rik, MAP syndrome, assay, growth, Muscle Tissue, Laboratory Mouse, B230107K20Rik, FAP2, colorectal adenomatous polyposis, skeletal muscle systemGene., dorsal tube, vertebrate heart, Membranes, RGD1304931, Mitochondrial, Outer Mitochondrial, outer mitochondrial membrane, Herz, C1orf170, Outer Mitochondrial Membranes, Outer, heart or heart like organ, protein complex, Inner, Proteins, adult heart, branchial heart, proteins, Hearts, protein, cardiac structure, Membrane, protein-containing complex, Mitochondrial Membrane, Outer Mitochondrial Membrane, Protein Gene Products, Gene Proteins, circulatory vessel, cardiac pump, protein polypeptide chains, chambered heart, Mitochondrial Membranes, native protein, natural protein, polypeptide chain, Inner Mitochondrial Membrane, Inner Mitochondrial, heart, Inner Mitochondrial Membranes, Protein, Gene Products, 2310042D19Rik, cardium, protein aggregate, outer mitochondrion membrane, mitochondrion outer membraneGene., dorsal 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Mus domesticus, Aminosaeure, Anterior Tibial Muscle, Uros1, Amino acid, CAT-1, adult heart, growth and development, CASP-14, protein, Mitochondrial Contractions, House Mouse, phosphorylation, prevention, BB129864, circulatory vessel, protein polypeptide chains, Mitochondrial Membranes, A830037N07Rik, PGC-1v, 2, Kinase, protein aggregate, Fs(3)Hor, prevention and control, peptidase M activity, mitochondrion outer membrane, adenomas, rabGAPLP, L-methionine aminopeptidase activity, DmelCG2684, Muscle Tissues, amino acids, malignant fibrohistiocytic tumours, reference sample, heart or heart like organ, Gm11133, dERR, Tissue, AI839531, CG7404, T25658, hypoplasia, RabGAP-5, Swiss Mice, proteins, purification, NTef2, cardiac structure, inhibition of homeostatic process, infection by Yersinia pestis, 2610002D09Rik, preventive measures, isolation and purification, Muscles, Inner Mitochondrial Membrane, PBGD, RUSC3, homeostasis, 2610009E16Rik, cardiac morphogenesis, ATP Phosphotransferases, Ppargc1, outer mitochondrion membrane, Gastrocnemius, AI323697, ATP, dorsal tube, vertebrate heart, preventive therapy, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma/high-grade spindle cell sarcoma, Aminokarbonsaeure, MYH-associated polyposis, mouse, autosomal recessive familial adenomatous polyposis, Maps, Mitochondrial Protein, Phosphatides, results, alpha-amino carboxylic acids, Fs(3)Sz11, Pgc1, chambered heart, positive regulation of homeostatic process, Voluntary Muscle, Solute carrier family 7 member 1, Voluntary, Mini-ICE, Inner Mitochondrial Membranes, Lipid, Voluntary Muscles, simple tissue, cardium, ATRC1, regulator, autosomal recessive, ARALAR, ParaT, Mus musculus, Amino Acid, Acid, RUTBC3, Transphosphorylases, Mitochondrial, ENSMUSG00000079510, Caspase-14 subunit p10, Amino acids, Outer, mice, cardiac myocyte proliferation, Swiss Mouse, heart muscle cell proliferation, malignant fibrohistiocytic tumors, Caspase-14 subunit p19, MICE, early, muscle 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Ecotropic retrovirus receptor, musculus, negative regulation of homeostatic process, species, Ecotropic retroviral leukemia receptor, Anterior Tibial, Controlled, striated muscle, small, Autoregulation, Controlling, MUTYH-Associated Polyposis, protein complex, Carnitine palmitoyltransferase II (CPT II) deficiency, CPTASE, Proteins, Phosphorylations, HCAT1, CPT1, Hearts, alpha-amino acids, Mitochondrial., Muscle, motif, cardiac development, Phosphotransferases, Lipin-1, Pgc-1alpha, development, Soleus, Contractions, somatic muscle, 3.1.3.4, native protein, natural protein, Mus, Protein, chemical analysis, heart, regulation of homeostatic process, Membranes, a phospholipid derivative, Soleus Muscle, underdeveloped, Kinases, prophylaxis, postnatal growth, House Mice, muscle, MYH-Associated Polyposis, Membrane, Amino, Lds, Laboratory Mice, Protein Gene Products, Outer Mitochondrial Membrane, Mitochondrial Contraction, Gene Proteins, mitochondria, activation of homeostatic process, control, Inner Mitochondrial, dorsal vessel development, 2310042D19Rik, MAP syndrome, assay, growth, Muscle Tissue, Laboratory Mouse, B230107K20Rik, FAP2, colorectal adenomatous polyposis, skeletal muscle system0PXD020469falsePhosphoproteomics of the developing heart identifies PERM1 - an outer mitochondrial membrane proteinHeart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein kinase 2. Ablation of Perm1 in mice results in reduced protein expression of lipin-1 accompanied by accumulation of specific phospholipid species. Isolation of Perm1-deficient mitochondria revealed significant downregulation of mitochondrial transport proteins for amino acids and carnitines, including SLC25A12/13/29/34 and CPT2. Consistently, we observed altered levels of various lipid species, amino acids and acylcarnitines in Perm1-/- mitochondria. We conclude that the outer mitochondrial membrane protein PERM1 regulates homeostasis of lipid and amino acid metabolites in mitochondria.Tue Jul 21 04:20:00 BST 2020MSV00008579633549681