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Polten"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"software":[""],"submitter_keywords":["Heart","Rhot1","Rhot2","Mouse"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD069555"],"tissue":["Heart"],"sample_protocol":["After tissue harvest, hearts were quickly washed in ice-cold PBS, snap-frozen in liquid nitrogen, and stored at -80°C until subjected to further analysis. For 1-day-old mice, three animals per sample were pooled. Cardiac tissue was resuspended in 500 µL of Urea buffer supplemented with phosphatase and protease inhibitors. Protein extracts were reduced by incubating with 5 mmol/L DTT for 60 minutes at 37°C and alkylated by adding 10 mmol/L iodacetamide. Protein samples were diluted 1:5 with 50 mmol/L sodium bicarbonate buffer and digested in solution using LysC (1:100) for 4 hours at 37°C, which was followed by further trypsin digestion (1:50) at 37°C overnight. Protein digests were desalted using C18 spin tips. Eluted peptides were subjected to phosphopeptide enrichment, followed by TMT labeling and liquid chromatography-mass spectrometry (LC-MS) measurements."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Database search was performed against reviewed human entries of Uniprot DB using MaxQuant (version 2.0.1.0). Protein identification was controlled by FDR<0.01 at the protein and peptide level."],"omics_type":["Proteomics"],"labhead":["Christian Riehle"],"instrument_platform":[""],"labhead_affiliation":["Hannover Medical School, Department of Cardiology and Angiology"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"submitter_mail":["polten.felix@mh-hannover.de"],"publication":["41834725 Froese N, Shymotiuk I, Froese A, Polten F, Jablinski J, Scholz T, Korf-Klingebiel M, Werlein C, Galuppo P, Gigina A, Wihler K, Schneider J, Erschow S, Heimerl M, Szaroszyk M, Hegermann J, Wrede C, Schweitzer T, Pich A, Geffers R, Ricke-Hoch M, Kühnel MP, Jonigk DD, Wende AR, Abel ED, Nikolaev VO, Wollert KC, Bauersachs J, Riehle C. RHOT Proteins Link Mitochondrial Motility to Cardiomyocyte Sarcomere Maturation. Circ Res. 2026 138(9):e327297 10.1161/circresaha.125.327297"],"submitter_affiliation":["Hanover Medical School - Division of Molecular and Translational Cardiology"],"submitter_country":["Germany"],"pubmed_abstract":["<h4>Background</h4>Cardiomyocyte mitochondria align with sarcomeres during heart development. Mitochondrial motility is controlled by RHOT (ras homolog family member T) 1 and RHOT2. RHOT1 and RHOT2 are atypical Rho-like small GTPases that are anchored to the outer mitochondrial membrane and couple mitochondria to kinesin and dynein motors. We hypothesized that RHOT protein expression and mitochondrial motility are required for mitochondrial positioning during cardiomyocyte development.<h4>Methods</h4>We generated mice with cardiomyocyte-selective deletion of <i>Rhot1</i> and <i>Rhot2</i> during embryogenesis (cRhot1/2-KO [constitutive and embryonic cardiomyocyte-selective <i>Rhot1</i>/2 knockout]) or tamoxifen-inducible deletion in the adult heart (iRhot1/2-KO [inducible cardiomyocyte-selective <i>Rhot1/2</i> knockout]) to assess the importance of mitochondrial motility during and after cardiomyocyte maturation. Mitochondrial motility was determined by a motor protein-driven single mitochondria motility assay. Respiratory capacity was measured in isolated mitochondria. Intracellular mitochondrial localization and ATP production in isolated cardiomyocytes were assessed by confocal microscopy and after adenoviral expression of the fluorescence resonance energy transfer-based ATP biosensor ATeam. Cardiac ultrastructure was assessed by electron micrographs; mass spectrometry was used for proteome analysis.<h4>Results</h4>cRhot1/2-KO mice developed fatal cardiomyopathy associated with sarcomere disarray and perinuclear accumulation of mitochondria and ATP production. Mitochondria isolated from cRhot1/2-KO hearts exhibited impaired motility but preserved respiratory capacity. Mechanistically, proteome analysis identified that RHOT proteins bind mitochondria to contractile muscle fiber proteins. In contrast, inducible deletion of <i>Rhot1</i> and <i>Rhot2</i> in adult iRhot1/2-KO mice did not result in heart failure. Despite impaired motility of isolated mitochondria, intracellular mitochondrial localization, local ATP production, and sarcomere structure were preserved in adult iRhot1/2-KO hearts after cardiomyocyte maturation.<h4>Conclusions</h4>RHOT proteins bind mitochondria to contractile muscle fiber proteins and are required for mitochondrial positioning in cardiomyocytes during development. Our study links mitochondrial motility and local ATP production to structural and functional maturation of the heart."],"pubmed_title":["RHOT Proteins Link Mitochondrial Motility to Cardiomyocyte Sarcomere Maturation."],"pubmed_authors":["Froese Natali N, Shymotiuk Ivanna I, Froese Alexander A, Polten Felix F, Jablinski Jonas J, Scholz Tim T, Korf-Klingebiel Mortimer M, Werlein Christopher C, Galuppo Paolo P, Gigina Anna A, Wihler Katharina K, Schneider Johanna J, Erschow Sergej S, Heimerl Maren M, Szaroszyk Malgorzata M, Hegermann Jan J, Wrede Christoph C, Schweitzer Theresa T, Pich Andreas A, Geffers Robert R, Ricke-Hoch Melanie M, Kühnel Mark P MP, Jonigk Danny D DD, Wende Adam R AR, Abel E Dale ED, Nikolaev Viacheslav O VO, Wollert Kai C KC, Bauersachs Johann J, Riehle Christian C"],"additional_accession":[]},"is_claimable":false,"name":"RHOT proteins link mitochondrial motility to cardiomyocyte sarcomere maturation.","description":"Proteome and phosphoproteome analysis of left ventricular tissue obtained from mice with embryonic, cardiomyocyte-selective deletion of Rhot1/2 (cRhot1/2-KO) and controls (cRhot1/2-Con) at 1-day and 4-weeks of age.","dates":{"publication":"2026-04-30","submission":"2025-10-16"},"accession":"PXD069555","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:36630","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:237610","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:491","NEWT:460523","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:1640278","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:906914","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:10832","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:475932","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:28550","NEWT:80863","NEWT:90675","NEWT:52639","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1045775","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:99488","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:1028307","NEWT:13489","NEWT:29829","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:441772","NEWT:48106","NEWT:202956","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","N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