title: Mitochondrial DNA copy number and biogenesis in different tissues of early- and late-lactating dairy cows.
abstract: Energy balance in dairy cows changes during the course of lactation due to alterations in voluntary feed intake and energy required for milk synthesis. To adapt to the demands of lactation, energy metabolism needs to be regulated and coordinated in key organs such as adipose tissue (AT), liver, and mammary gland. Mitochondria are the main sites of energy production in mammalian cells and their number varies depending on age, organ, and physiological condition. The copy number of the mitochondrial genome, the mitochondrial DNA (mtDNA), reflects the abundance of mitochondria within a cell and is regulated by transcriptional and translational factors. Environmental, physiological, and energetic conditions change during lactation and we thus hypothesized that these changes may influence the mtDNA copy number and the abundance of genes regulating mitochondrial biogenesis. Therefore, we aimed to provide an overview of mitochondrial biogenesis in liver, subcutaneous (sc)AT, mammary gland, and peripheral blood cells during early and late lactation in dairy cows. German Holstein cows (n=21) were fed according to their requirements, and biopsies from scAT, liver, mammary gland, and blood were collected in early and late lactation and assayed for relative mtDNA copy numbers and the mRNA abundance of genes regulating mitochondrial biogenesis, such as nuclear-respiratory factor 1 and 2 (NRF-1, NRF-2), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α). The number of mtDNA copies increased from early to late lactation in all tissues, whereas that in peripheral blood cells was greater in early compared with late lactation. Moreover, mitochondrial activity enzymes (i.e., citrate synthase and cytochrome c oxidase) increased from early to late lactation in scAT. Comparing the number of mtDNA copies between tissues and blood in dairy cows, the highest mtDNA content was observed in liver. The mRNA abundance of genes related to mitochondrial biogenesis changed in a tissue-specific manner when comparing early versus late lactation. The mtDNA copy number was associated with transcriptional factors only in AT, suggesting nontranscriptional regulation of mtDNA in the other tissues. We detected strong correlations between peripheral blood mtDNA and tissue mtDNA content in early lactation. Peripheral blood forms an appropriate medium to display the cellular content of mtDNA copy numbers and consequently the cellular energy status of tissues during early lactation.
authors.affiliation: Institute of Animal Science, Physiology and Hygiene Unit, University of Bonn, 53115 Bonn, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Laubenthal
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Unit, University of Bonn, 53115 Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hoelker
authors.affiliation: Institute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, 38116 Braunschweig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Frahm
authors.affiliation: Institute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, 38116 Braunschweig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dänicke
authors.affiliation: Institute of Animal Science, Animal Nutrition Group, University of Bonn, 53115 Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Gerlach
authors.affiliation: Institute of Animal Science, Animal Nutrition Group, University of Bonn, 53115 Bonn, Germany.
authors.forename: K-H
authors.initials: KH
authors.lastname: Südekum
authors.affiliation: Institute of Animal Science, Physiology and Hygiene Unit, University of Bonn, 53115 Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Sauerwein
authors.affiliation: Institute of Animal Science, Physiology and Hygiene Unit, University of Bonn, 53115 Bonn, Germany. Electronic address: susanne.haeussler@uni-bonn.de.
authors.forename: S
authors.initials: S
authors.lastname: Häussler
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002417:Cattle / Q000235:genetics / Q000502:physiology*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D007774:Lactation; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D008892:Milk / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C422562:mitochondrial transcription factor A
keywords: dairy cow; mitochondrial DNA copy number; mitochondrial biogenesis