Differential Alterations of the Mitochondrial Morphology and Respiratory Chain Complexes during Postnatal Development of the Mouse Lung

Mitochondrial biogenesis and adequate energy production in various organs of mammals are necessary for postnatal adaptation to extrauterine life in an environment with high oxygen content. Even though transgenic mice are frequently used as experimental models, to date, no combined detailed molecular and morphological analysis on the mitochondrial compartment in different lung cell types has been performed during postnatal mouse lung development. In our study, we revealed a significant upregulation of most mitochondrial respiratory complexes at protein and mRNA levels in the lungs of P15 and adult animals in comparison to newborns. The majority of adult animal samples showed the strongest increase, except for succinate dehydrogenase protein (SDHD). Likewise, an increase in mRNA expression for mtDNA transcription machinery genes (Polrmt, Tfam, Tfb1m, and Tfb2m), mitochondrially encoded RNA (mt-Rnr1 and mt-Rnr2), and the nuclear-encoded mitochondrial DNA polymerase (POLG) was observed. The biochemical and molecular results were corroborated by a parallel increase of mitochondrial number, size, cristae number, and complexity, exhibiting heterogeneous patterns in distinct bronchiolar and alveolar epithelial cells. Taken together, our results suggest a specific adaptation and differential maturation of the mitochondrial compartment according to the metabolic needs of individual cell types during postnatal development of the mouse lung.

[1]  T. Mariani,et al.  Postnatal development of the bronchiolar club cells of distal airways in the mouse lung: stereological and molecular biological studies , 2016, Cell and Tissue Research.

[2]  Prashant Mishra,et al.  Mitochondrial dynamics and inheritance during cell division, development and disease , 2014, Nature Reviews Molecular Cell Biology.

[3]  G. Washko,et al.  Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. , 2014, The Journal of clinical investigation.

[4]  V. Ten,et al.  Mechanical ventilation causes pulmonary mitochondrial dysfunction and delayed alveolarization in neonatal mice. , 2013, American journal of respiratory cell and molecular biology.

[5]  Katsutoshi Nakayama,et al.  Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence. , 2013, American journal of physiology. Lung cellular and molecular physiology.

[6]  Michael A Thompson,et al.  Mitochondria in lung diseases , 2013, Expert review of respiratory medicine.

[7]  P. Kirkham,et al.  Oxidative stress in COPD. , 2013, Chest.

[8]  P. Thomas,et al.  Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer. , 2013, Respiratory medicine.

[9]  P. Diemunsch,et al.  Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target , 2013, Experimental physiology.

[10]  K. J. Thomas,et al.  The role of mitochondria in the development and progression of lung cancer , 2013, Computational and structural biotechnology journal.

[11]  B. Rothermel,et al.  Cell death and survival through the endoplasmic reticulum-mitochondrial axis. , 2012, Current molecular medicine.

[12]  Nektarios Tavernarakis,et al.  Downregulation of lung mitochondrial prohibitin in COPD. , 2012, Respiratory medicine.

[13]  C. Roussos,et al.  Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma , 2012, PloS one.

[14]  T. Boettger,et al.  Oxidative stress during mitochondrial biogenesis compromises mtDNA integrity in growing hearts and induces a global DNA repair response , 2012, Nucleic acids research.

[15]  Y. E. Chen,et al.  Mitochondrial Dysfunction and Adipogenic Reduction by Prohibitin Silencing in 3T3-L1 Cells , 2012, PloS one.

[16]  H. McBride,et al.  A Vesicular Transport Pathway Shuttles Cargo from Mitochondria to Lysosomes , 2012, Current Biology.

[17]  Martin J. Mueller,et al.  Sam50 Functions in Mitochondrial Intermembrane Space Bridging and Biogenesis of Respiratory Complexes , 2012, Molecular and Cellular Biology.

[18]  P. Pinton,et al.  Mitochondrial calcium homeostasis as potential target for mitochondrial medicine , 2012, Mitochondrion.

[19]  S. Jakobs,et al.  Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA , 2011, Proceedings of the National Academy of Sciences.

[20]  S. Weitzman,et al.  Chronic inflammation and cancer: the role of the mitochondria. , 2011, Oncology.

[21]  M. Schuelke,et al.  Region-Specific Expression of Mitochondrial Complex I Genes during Murine Brain Development , 2011, PloS one.

[22]  Yuichi Matsushima,et al.  Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM) , 2010, Proceedings of the National Academy of Sciences.

[23]  M. Tesařová,et al.  Mitochondrial DNA content and expression of genes involved in mtDNA transcription, regulation and maintenance during human fetal development. , 2010, Mitochondrion.

[24]  Rouslan G. Efremov,et al.  The architecture of respiratory complex I , 2010, Nature.

[25]  C. Gustafsson,et al.  Human Mitochondrial Transcription Revisited , 2010, The Journal of Biological Chemistry.

[26]  B. Larsson,et al.  THE POSTNATAL DEVELOPMENT OF THE MITOCHONDRIAL CONTENTS IN BLOOD LYMPHOCYTES OF NORMAL AND OXYGEN-EXPOSED MICE. , 2009, Acta pathologica et microbiologica Scandinavica.

[27]  H. Zentgraf,et al.  Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[28]  Justin R. Cross,et al.  ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation , 2009, Science.

[29]  S. Karnati,et al.  Peroxisomes in airway epithelia and future prospects of these organelles for pulmonary cell biology , 2009, Histochemistry and Cell Biology.

[30]  R. Polin,et al.  Mitochondrial dysfunction contributes to alveolar developmental arrest in hyperoxia-exposed mice. , 2009, American journal of respiratory cell and molecular biology.

[31]  Dean P. Jones Radical-free biology of oxidative stress. , 2008, American journal of physiology. Cell physiology.

[32]  S. Karnati,et al.  Peroxisomes in mouse and human lung: their involvement in pulmonary lipid metabolism , 2008, Histochemistry and Cell Biology.

[33]  A. Crofts,et al.  The Q-cycle reviewed: How well does a monomeric mechanism of the bc(1) complex account for the function of a dimeric complex? , 2008, Biochimica et biophysica acta.

[34]  Dudley Lamming,et al.  Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival , 2007, Cell.

[35]  Dean P. Jones,et al.  Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress. , 2007, Archives of biochemistry and biophysics.

[36]  C. Gustafsson,et al.  DNA replication and transcription in mammalian mitochondria. , 2007, Annual review of biochemistry.

[37]  S. Elmore Apoptosis: A Review of Programmed Cell Death , 2007, Toxicologic pathology.

[38]  M. Salathe,et al.  Regulation of mammalian ciliary beating. , 2007, Annual review of physiology.

[39]  D. Chan Mitochondria: Dynamic Organelles in Disease, Aging, and Development , 2006, Cell.

[40]  L. Murphy,et al.  The Prohibitins: emerging roles in diverse functions , 2006, Journal of cellular and molecular medicine.

[41]  R. Iida,et al.  Quantitative change in mitochondrial DNA content in various mouse tissues during aging. , 2005, Biochimica et biophysica acta.

[42]  P. Mitchell,et al.  MELAS A3243G mitochondrial DNA mutation and age related maculopathy. , 2004, American journal of ophthalmology.

[43]  M. Carraway,et al.  Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis. , 2004, Cardiovascular research.

[44]  L. Blatter,et al.  Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells. , 2004, American journal of physiology. Cell physiology.

[45]  Stephan Immenschuh,et al.  Differential Cellular and Subcellular Localization of Heme-Binding Protein 23/Peroxiredoxin I and Heme Oxygenase-1 in Rat Liver , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[46]  G. Cecchini,et al.  Function and structure of complex II of the respiratory chain. , 2003, Annual review of biochemistry.

[47]  M. Zeviani,et al.  Mitochondrial disorders. , 2004, Brain : a journal of neurology.

[48]  K. Deichmann,et al.  Identification of common polymorphisms in the mitochondrial genome , 2003, Allergy.

[49]  C. Thompson,et al.  Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis , 2003, Cell Death and Differentiation.

[50]  I. Sato,et al.  NADH‐O2 oxidoreductase activity and mRNA expression of complex I (51 kDa, ND1) in postnatal intrinsic muscle of rat tongue , 2003, Journal of anatomy.

[51]  R. Radi,et al.  Peroxynitrite reactions and formation in mitochondria. , 2002, Free radical biology & medicine.

[52]  Yau-Huei Wei,et al.  Oxidative Stress , Mitochondrial DNA Mutation , and Impairment of Antioxidant Enzymes in Aging 1 , 2002 .

[53]  E. Gelfand Pro: mice are a good model of human airway disease. , 2002, American journal of respiratory and critical care medicine.

[54]  C. Gustafsson,et al.  Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA , 2002, Nature Genetics.

[55]  Khoon-Yen Tay,et al.  Genome-wide gene expression profiles of the developing mouse hippocampus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[56]  S. Dimauro,et al.  The genetics and pathology of oxidative phosphorylation , 2001, Nature Reviews Genetics.

[57]  B. Freeman,et al.  Reaction of Peroxynitrite with Mn-Superoxide Dismutase , 2001, The Journal of Biological Chemistry.

[58]  Heinz Fehrenbach,et al.  Alveolar epithelial type II cell: defender of the alveolus revisited , 2001, Respiratory research.

[59]  R. Gottlieb Mitochondria: execution central , 2000, FEBS letters.

[60]  K. Konishi,et al.  Developmental changes in enzyme activities and in morphology of rat cortex mitochondria. , 2000, Okajimas folia anatomica Japonica.

[61]  C. Richter,et al.  Nitric oxide synthase activity in mitochondria , 1997, FEBS letters.

[62]  P. Herpin,et al.  Postnatal changes in mitochondrial protein mass and respiration in skeletal muscle from the newborn pig. , 1997, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[63]  H. Schägger,et al.  Cytochrome-c oxidase in developing rat heart. Enzymic properties and amino-terminal sequences suggest identity of the fetal heart and the adult liver isoform. , 1995, European journal of biochemistry.

[64]  J. Marín-García,et al.  Mitochondrial gene expression during bovine cardiac growth and development. , 1994, Journal of Molecular and Cellular Cardiology.

[65]  R. Aggeler,et al.  Coupling between catalytic sites and the proton channel in F1F0-type ATPases. , 1994, Trends in biochemical sciences.

[66]  J. Walker,et al.  The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains , 1992, Quarterly Reviews of Biophysics.

[67]  E. Geshi,et al.  Postnatal changes in heart mitochondrial calcium and energy metabolism. , 1991, The American journal of physiology.

[68]  G. Sieck,et al.  Postnatal Changes in the Distribution of Succinate Dehydrogenase Activities among Diaphragm Muscle Fibers , 1991, Pediatric Research.

[69]  S. Young,et al.  Development of type II pneumocytes in rat lung. , 1991, The American journal of physiology.

[70]  D. Turnbull,et al.  6 Mitochondrial oxidations and ATP synthesis in muscle , 1990 .

[71]  B. Shapiro MITOCHONDRIAL DYSFUNCTION, ENERGY EXPENDITURE, AND CYSTIC FIBROSIS , 1988, The Lancet.

[72]  J. Satrústegui,et al.  Postnatal development of rat liver mitochondrial functions. The roles of protein synthesis and of adenine nucleotides. , 1988, The Journal of biological chemistry.

[73]  D. A. Clayton,et al.  Yeast mitochondrial RNA polymerase is homologous to those encoded by bacteriophages T3 and T7 , 1987, Cell.

[74]  D. Massaro,et al.  Development of bronchiolar epithelium in rats. , 1986, The American journal of physiology.

[75]  M. Denis,et al.  Structure and function of cytochrome-c oxidase. , 1986, Biochimie.

[76]  G. Danscher,et al.  Light microscopic visualization of colloidal gold on resin-embedded tissue. , 1983, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[77]  D. Hyde,et al.  Estimation of cell numbers and volumes of bronchiolar epithelium during rabbit lung maturation. , 1983, The American journal of anatomy.

[78]  C. Plopper,et al.  Cytodifferentiation of the nonciliated bronchiolar epithelial (Clara) cell during rabbit lung maturation: an ultrastructural and morphometric study. , 1983, The American journal of anatomy.

[79]  T. Yamamoto,et al.  Postnatal ontogenesis of hippocampal CA1 area in rats. I. Development of dendritic arborisation in pyramidal neurons , 1981, Brain Research Bulletin.

[80]  T. Yamamoto,et al.  Postnatal ontogenesis of hippocampal CA1 area in rats. II. Development of ultrastructure in stratum lacunosum and moleculare , 1981, Brain Research Bulletin.

[81]  Julio Montoya,et al.  tRNA punctuation model of RNA processing in human mitochondria , 1981, Nature.

[82]  G. Asimakis,et al.  Postnatal development of rat liver mitochondria: state 3 respiration, adenine nucleotide translocase activity, and the net accumulation of adenine nucleotides. , 1980, Archives of biochemistry and biophysics.

[83]  R. Sutton,et al.  Hormone-initiated maturation of rat liver mitochondria after birth. , 1980, The Biochemical journal.

[84]  N. Tolbert,et al.  Postnatal development of peroxisomal and mitochondrial enzymes in rat liver , 1979, Journal of cellular physiology.

[85]  R. Feigal,et al.  Mitrochondrial NADH dehydrogenase in cystic fibrosis. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[86]  J. K. Pollak The maturation of the inner membrane of foetal rat liver mitochondria. , 1975, The Biochemical journal.

[87]  D. Heath,et al.  The Clara cell , 1974, Thorax.

[88]  A. Fisher,et al.  Respiration of rat lung mitochondria and the influence of Ca 2+ on substrate utilization. , 1973, Biochemistry.

[89]  L. Flohé,et al.  [Glutathione peroxidase. IV. Intracellular distribution of the glutathione peroxidase system in the rat liver]. , 1971, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[90]  R. Toury,et al.  Etude de l'evolution des activites des enzymes mitochondriaux de l'hepatocyte au cours du developpement du rat , 1970 .

[91]  A. Baskerville Ultrastructural studies of the normal pulmonary tissue of the pig. , 1970, Research in veterinary science.

[92]  S. Sorokin Reconstructions of centriole formation and ciliogenesis in mammalian lungs. , 1968, Journal of cell science.

[93]  C. Lang RESPIRATORY ENZYMES IN THE HEART AND LIVER OF THE PRENATAL AND POSTNATAL RAT. , 1965, The Biochemical journal.

[94]  P. Mitchell Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism , 1961, Nature.

[95]  N. Parinandi,et al.  Mitochondrial Function in Lung Health and Disease , 2014 .

[96]  J. Houštěk,et al.  Developmental changes of cytochrome c oxidase and citrate synthase in rat heart homogenate. , 2004, Physiological research.

[97]  J. Drazen,et al.  Mouse models of airway responsiveness: physiological basis of observed outcomes and analysis of selected examples using these outcome indicators. , 1999, Annual review of physiology.

[98]  C. White,et al.  Loss of lung mitochondrial aconitase activity due to hyperoxia in bronchopulmonary dysplasia in primates. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[99]  K. J. Brooks,et al.  Postnatal development of the complexes of the electron transport chain in synaptic mitochondria from rat brain. , 1995, Developmental neuroscience.

[100]  S. Heales,et al.  Postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria. , 1994, Developmental neuroscience.

[101]  E. Kandel,et al.  Proceedings of the National Academy of Sciences of the United States of America. Annual subject and author indexes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[102]  H. Schägger,et al.  Isolation of the eleven protein subunits of the bc1 complex from beef heart. , 1986, Methods in enzymology.

[103]  R. Sutton,et al.  The differentiation of animal mitochondria during development , 1980 .

[104]  R. Toury,et al.  [Study on the evolution of mitochondrial enzyme activities in hepatocyte during rat development]. , 1970, Biochimica et biophysica acta.

[105]  G. Schatz,et al.  The biogenesis of mitochondria. , 1970, The Biochemical journal.

[106]  S. Sorokin Centriole formation and ciliogenesis. , 1968, Aspen Emphysema Conference.

[107]  Sorokin Sp Centriole formation and ciliogenesis. , 1968 .