title: Postnatal cardiomyocyte growth and mitochondrial reorganization cause multiple changes in the proteome of human cardiomyocytes.
abstract: Fetal (fCM) and adult cardiomyocytes (aCM) significantly differ from each other both by structure and biochemical properties. aCM own a higher mitochondrial mass compared to fCM due to increased energy demand and show a greater density and higher degree of structural organization of myofibrils. The energy metabolism in aCM relies virtually completely on β-oxidation of fatty acids while fCM use carbohydrates. Rewinding of the aCM phenotype (de-differentiation) arises frequently in diseased hearts spurring questions about its functional relevance and the extent of de-differentiation. Yet, surprisingly little is known about the changes in the human proteome occurring during maturation of fCM to aCM. Here, we examined differences between human fetal and adult hearts resulting in the quantification of 3500 proteins. Moreover, we analyzed mitochondrial proteomes from both stages to obtain more detailed insight into underlying biochemical differences. We found that the majority of changes between fCM and aCM were attributed to growth and maturation of cardiomyocytes. As expected, adult hearts showed higher mitochondrial mass and expressed increased levels of proteins involved in energy metabolism but relatively lower copy numbers of mitochondrial DNA (mtDNA) per total cell volume. We uncovered that the TFAM/mtDNA ratio was kept constant during postnatal development despite a significant increase of mitochondrial protein per mtDNA in adult mitochondria, which revises previous concepts.
authors: Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. Jaakko.Pohjoismaki@uef.fi
authors: Jaakko L O
authors: JL
authors: Pohjoismäki
authors: Marcus
authors: M
authors: Krüger
authors: Natalie
authors: N
authors: Al-Furoukh
authors: Anssi
authors: A
authors: Lagerstedt
authors: Pekka J
authors: PJ
authors: Karhunen
authors: Thomas
authors: T
authors: Braun
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D006801:Humans; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D020543:Proteome
chemical_list: D004272:DNA, Mitochondrial; D020543:Proteome