Abstract
Adequate metabolic adaptation of key tissues playing an essential role for bioenergetic homeostasis and lactogenesis is critical in cows to adapt to changes in energy requirements and physiological processes during the lactation period. Mitochondria are recognized as central to meet energy needs and maintaining of metabolic homeostasis because mitochondrial DNA (mtDNA) is template for several polypeptides of the respiratory chain complexes essential for ATP generation. The quantity of mtDNA in a cell has been widely used as a surrogate marker for the capacity of cells for energy generation. In our study we analyzed the mtDNA copy number and the mRNA expression of important nuclear encoded genes controlling mitochondrial biogenesis in liver and mammary gland. We compared cows with a nuclear genome dairy × beef crossbred make-up to purebred German Holstein dairy cows. The study revealed tissue-specific variations of mtDNA copy number and expression levels of nuclear genes involved in mitochondrial biogenesis when comparing lactating cows with different genetic predisposition regarding milk performance. This may reflect nuclear genome-determined genetic differences between the cow groups in coping with metabolic demands and physiological changes during lactation. The results indicate that mitochondrial biogenesis processes in the liver and mammary gland appear to be impaired in high lactating dairy cows, which consequently, would point to a disturbed energy adaptation. The results provide a basis to further elucidate the adaptive and regulatory modulation of the mitochondrial biogenesis in response to lactation-associated metabolic challenges in lactating cows.
Similar content being viewed by others
References
Loor J (2010) Genomics of metabolic adaptations in the peripartal cow. Animal 4:1110–1139
White HM (2015) The role of TCA cycle anaplerosis in ketosis and fatty acid liver in periparturient dairy cows. Animals 5:793–802
Cheng Z, Ristow M (2013) Mitochondria and metabolic homeostasis. Antioxid Redox Signal 19:240–242
Montgomery MK, Turner N (2015) Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect 4:R1–R15
Duarte FV, Amorim JA, Palmeira CM, Rolo AP (2015) Regulation of mitochondrial function and its impact in metabolic stress. Curr Med Chem 22:2468–2479
Gonzalez-Freire M, de Cabo R, Bernier M, Sollott SJ, Fabbri E, Navas P et al (2015) Reconsidering the role of mitochondria in aging. J Gerontol A Biol Sci Med Sci 70:1334–1342
Wang CH, Wu SB, Wu YT, Wei YH (2013) Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med 238:450–460
Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336
Guha M, Avadhani NG (2013) Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion 13:577–591
Pieczenik SR, Neustadt J (2007) Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83:84–92
Lee HC, Wei YH (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 37:822–834
Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368
Scarpulla RC, Vega RB, Kelly DP (2012) Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab 23:459–466
Dominy JE, Puigserver P (2013) Mitochondrial biogenesis through activation of nuclear signaling proteins. Cold Spring Harb Perspect Biol 5:a015008
Cannino G, Di Liegro CM, Rinaldi AM (2007) Nuclear-mitochondrial interaction. Mitochondrion 7:359–366
Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1 alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884S–890S
Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638
Theilen NT, Kunkel GH, Tyagi SC (2017) The role of exercise and TFAM in preventing skeletal muscle atrophy. J 232:2348–2358
Montier LLC, Deng JJ, Bai YD (2009) Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genom 36:125–131
Suhm T, Ott M (2017) Mitochondrial translation and cellular stress response. Cell Tissue Res 367:21–31
Chinnery PF, Hudson G (2013) Mitochondrial genetics. Br Med Bull 106:135–159
D’Erchia AM, Atlante A, Gadaleta G, Pavesi G, Chiara M, De Virgilio C et al (2015) Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity. Mitochondrion 20:13–21
Gilkerson R, Bravo L, Garcia I, Gaytan N, Herrera A, Maldonado A et al (2013) The mitochondrial nucleoid: integrating mitochondrial DNA into cellular homeostasis. Cold Spring Harb Perspect Biol 5:a011080
Picard M, Turnbull DM (2013) Linking the metabolic state and mitochondrial DNA in chronic disease. Health Aging Diabetes 62:672–678
Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125:1241–1252
Westermann B (2012) Bioenergetic role of mitochondrial fusion and fission. Biochim Biophys Acta Bioenerg 1817:1833–1838
Gomes LC, Scorrano L (2011) Mitochondrial elongation during autophagy A stereotypical response to survive in difficult times. Autophagy 7:1251–1253
Liesa M, Shirihai OS (2013) Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 17:491–506
Ryan MT, Hoogenraad NJ (2007) Mitochondrial-nuclear communications. Annu Rev Biochem 76:701–722
Hadsell DL, Olea W, Wei J, Fiorotto ML, Matsunami RK, Engler DA et al (2011) Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle. Physiol Genom 43:271–285
Laubenthal L, Hoelker M, Frahm J, Daenicke S, Gerlach K, Suedekum K et al (2016) Mitochondrial DNA copy number and biogenesis in different tissues of early- and late-lactating dairy cows. J Dairy Sci 99:1571–1583
Kühn Ch, Bellmann O, Voigt J, Wegner J, Guiard V, Ender K (2002) An experimental approach for studying the genetic and physiological background of nutrient transformation in cattle with respect to nutrient secretion and accretion type. Arch Anim Breed 45:317–330
Weikard R, Goldammer T, Brunner R, Kuehn C (2012) Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows. Physiol Genom 44:728–739
Hammon HM, Metges CC, Schulz A, Junghans P, Steinhoff J, Schneider F et al (2010) Differences in milk production, glucose metabolism, and carcass composition of 2 Charolais × Holstein F2 families derived from reciprocal paternal and maternal grandsire crosses. J Dairy Sci 93:3007–3018
Hammon HM, Bellmann O, Voigt J, Schneider F, Kuhn C (2007) Glucose-dependent insulin response and milk production in heifers within a segregating resource family population. J Dairy Sci 90:3247–3254
Pareek N, Voigt J, Bellmann O, Schneider F, Hammon HM (2007) Energy and nitrogen metabolism and insulin response to glucose challenge in lactating German Holstein and Charolais heifers. Livestock Sci 112:115–122
Hamada M, Albrecht E, El Bagory AR, Edris AB, Hammon HM, Nuernberg G et al (2012) Meat quality traits and muscle composition of cows differing in lactation performance. Arch Anim Breed 55:36–47
Kirchgessner M (1997) Tierernährung. Verlags Union Agrar, DLG Verlags GmbH, Frankfurt a. M.
McCarthy S, Waters S, Kenny D, Diskin M, Fitzpatrick R, Patton J et al (2010) Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: a global approach. Physiol Genom 42A:188–199
McCabe M, Waters S, Morris D, Kenny D, Lynn D, Creevey C (2012) RNA-seq analysis of differential gene expression in liver from lactating dairy cows divergent in negative energy balance. BMC Genom 13:193
Loor JJ, Everts RE, Bionaz M, Dann HM, Morin DE, Oliveira R et al (2007) Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows. Physiol Genom 32:105–116
Wathes D (2012) Mechanisms linking metabolic status and disease with reproductive outcome in the dairy cow. Reprod Dom Anim 47:304–312
Huber K, Daenicke S, Rehage J, Sauerwein H, Otto W, Rolle-Kampczyk U et al (2016) Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows. Sci Rep 6:24642
Qu B, Jiang Y, Zhao F, Xiao J, Li QZ (2012) Changes of endoplasmic reticulum and mitochondria in mammary epithelial cells during mammogenesis in Chinese Holstein dairy cows. Acta Histochem 114:448–453
Alex A, Collier J, Hadsell D, Collier R (2015) Milk yield differences between 1x and 4x milking are associated with changes in mammary mitochondrial number and milk protein gene expression, but not mammary cell apoptosis or SOCS gene expression. J Dairy Sci 98:4439–4448
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J et al (2003) PGC-1 alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273
Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471
Abuelo A, Hernandez J, Benedito JL, Castillo C (2016) Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study. J Anim Physiol Anim Nutr 100:279–286
Holtenius P, Holtenius K (1996) New aspects of ketone bodies in energy metabolism of dairy cows: a review. J Vet Med A Physiol Pathol Clin Med 43:579–587
Austin S, St-Pierre J (2012) PGC1 alpha and mitochondrial metabolism—emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125:4963–4971
Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K et al (2004) Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 13:935–944
Virbasius JV, Scarpulla RC (1994) Activation of the human mitochondrial transcription factor a gene by nuclear respiratory factors—a potential regulatory link between nuclear and mitochondrial gene-expression in organelle biogenesis. Proc Natl Acad Sci USA 91:1309–1313
Ikeda M, Ide T, Fujino T, Arai S, Saku K, Kakino T et al (2015) Overexpression of TFAM or twinkle increases mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. PLoS ONE 10:e0119687
Xu S, Zhong M, Zhang L, Wang Y, Zhou Z, Hao Y et al (2009) Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells. FEBS J 276:4224–4233
Picca A, Lezza AMS (2015) Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions Useful insights from aging and calorie restriction studies. Mitochondrion 25:67–75
Nicholls DG (2002) Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int J Biochem Cell Biol 34:1372–1381
Acknowledgements
We are grateful to our colleagues at the FBN Dummerstorf, who were engaged in the generation, care and sample collection of the SEGFAM F2 resource population for their constant support of our work, and we thank Astrid Kühl and Simone Wöhl for their excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Weikard, R., Kuehn, C. Different mitochondrial DNA copy number in liver and mammary gland of lactating cows with divergent genetic background for milk production. Mol Biol Rep 45, 1209–1218 (2018). https://doi.org/10.1007/s11033-018-4273-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-018-4273-x