Aravamudhan, Sriram, Turk, Clara, Bock, Theresa ORCID: 0000-0002-8308-4021, Keufgens, Lena ORCID: 0000-0001-6892-7302, Nolte, Hendrik, Lang, Franziska, Krishnan, Ramesh Kumar, Konig, Tim ORCID: 0000-0002-3484-1196, Hammerschmidt, Philipp, Schindler, Natalie ORCID: 0000-0001-7281-4597, Brodesser, Susanne, Rozsivalova, Dieu Hien, Rugarli, Elena, Trifunovic, Aleksandra, Bruening, Jens, Langer, Thomas, Braun, Thomas and Krueger, Marcus (2021). Phosphoproteomics of the developing heart identifies PERM1-An outer mitochondrial membrane protein. J. Mol. Cell. Cardiol., 154. S. 41 - 60. OXFORD: ELSEVIER SCI LTD. ISSN 1095-8584

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Abstract

Heart 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Aravamudhan, SriramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turk, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bock, TheresaUNSPECIFIEDorcid.org/0000-0002-8308-4021UNSPECIFIED
Keufgens, LenaUNSPECIFIEDorcid.org/0000-0001-6892-7302UNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krishnan, Ramesh KumarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konig, TimUNSPECIFIEDorcid.org/0000-0002-3484-1196UNSPECIFIED
Hammerschmidt, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schindler, NatalieUNSPECIFIEDorcid.org/0000-0001-7281-4597UNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rozsivalova, Dieu HienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-596943
DOI: 10.1016/j.yjmcc.2021.01.010
Journal or Publication Title: J. Mol. Cell. Cardiol.
Volume: 154
Page Range: S. 41 - 60
Date: 2021
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1095-8584
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OXIDATIVE CAPACITY; MASS-SPECTROMETRY; MOUSE; PHOSPHORYLATION; CARDIOMYOCYTE; FAMILY; TRANSPORTER; EXPRESSION; MUTATIONS; SEQUENCESMultiple languages
Cardiac & Cardiovascular Systems; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59694

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