scholarly journals Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1241-1252 ◽  
Author(s):  
D P Yakubu ◽  
A Mostyn ◽  
V Wilson ◽  
S Pearce ◽  
M C Alves-Guerra ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Late Pregnancy ◽  
Mitochondrial Proteins ◽  
Nutrient Restriction ◽  
Voltage Dependent Anion Channel ◽  
Pregnant Sheep ◽  
Liver And Kidney

Adaptation to the extrauterine environment at birth relies upon the onset of postnatal function and increased metabolism in the lungs, liver and kidney, mediated partly by activation of mitochondrial proteins such as the voltage-dependent anion channel (VDAC), cytochromecand, in the lung only, uncoupling protein (UCP)2. The magnitude of adaptation is dependent on the maternal metabolic and endocrine environment. We, therefore, examined the influence of maternal cold exposure (MCE) induced by winter shearing of pregnant sheep in conjunction with nutrient restriction (NR; 50% reduction in maternal food intake from 110 days gestation up to term). The effect of parity was also examined, as the offspring of nulliparous mothers are growth restricted compared with multiparous offspring. All sheep were twin bearing. One twin was sampled after birth and its sibling at 30 days. In the lung, both MCE and maternal nulliparity enhanced UCP2 abundance. However, whilst VDAC abundance was decreased in both the offspring of nulliparous mothers and by NR, it was transiently raised by MCE. Kidney VDAC abundance was reduced by MCE and nulliparity, adaptations only influenced by NR in multiparous mothers. Cytochromecabundance was raised by MCE and by NR in multiparous controls and raised in offspring of nulliparous mothers. Liver VDAC and cytochromecabundance were transiently reduced by MCE and persistently lower in offspring of nulliparous mothers. In conclusion, changes in the maternal metabolic environment have marked tissue-specific effects on mitochondrial protein abundance in the lungs, liver and kidney that may be important in enabling the newborn to effectively adapt to the extrauterine environment.

scholarly journals Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development

2005 ◽  
Vol 187 (1) ◽  
pp. 81-88 ◽  
Author(s):  
M G Gnanalingham ◽  
A Mostyn ◽  
J Wang ◽  
R Webb ◽  
D H Keisler ◽  
...  
Keyword(s):  
Protein Function ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Later Life ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Voltage Dependent Anion Channel ◽  
Tissue Specific ◽  
The Brain

Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 μg leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.

scholarly journals Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung

Reproduction ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 823-830 ◽  
Author(s):  
D P Yakubu ◽  
A Mostyn ◽  
M A Hyatt ◽  
L O Kurlak ◽  
H Budge ◽  
...  
Keyword(s):  
Mitochondrial Protein ◽  
Anion Channel ◽  
Functional Adaptation ◽  
Mitochondrial Proteins ◽  
Nutrient Restriction ◽  
Protein Abundance ◽  
Voltage Dependent Anion Channel ◽  
Tissue Specific ◽  
Nutritional Programming ◽  
Kidney Liver

This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochromec, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term ~147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochromecabundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.

Multifaceted roles of porin in mitochondrial protein and lipid transport

2019 ◽  
Vol 47 (5) ◽  
pp. 1269-1277 ◽  
Author(s):  
Toshiya Endo ◽  
Haruka Sakaue
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Lipid Transport ◽  
Mitochondrial Proteins ◽  
Carrier Protein ◽  
Intermembrane Space ◽  
Voltage Dependent Anion Channel ◽  
Tom Complex

Abstract Mitochondria are essential eukaryotic organelles responsible for primary cellular energy production. Biogenesis, maintenance, and functions of mitochondria require correct assembly of resident proteins and lipids, which require their transport into and within mitochondria. Mitochondrial normal functions also require an exchange of small metabolites between the cytosol and mitochondria, which is primarily mediated by a metabolite channel of the outer membrane (OM) called porin or voltage-dependent anion channel. Here, we describe recently revealed novel roles of porin in the mitochondrial protein and lipid transport. First, porin regulates the formation of the mitochondrial protein import gate in the OM, the translocase of the outer membrane (TOM) complex, and its dynamic exchange between the major form of a trimer and the minor form of a dimer. The TOM complex dimer lacks a core subunit Tom22 and mediates the import of a subset of mitochondrial proteins while the TOM complex trimer facilitates the import of most other mitochondrial proteins. Second, porin interacts with both a translocating inner membrane (IM) protein like a carrier protein accumulated at the small TIM chaperones in the intermembrane space and the TIM22 complex, a downstream translocator in the IM for the carrier protein import. Porin thereby facilitates the efficient transfer of carrier proteins to the IM during their import. Third, porin facilitates the transfer of lipids between the OM and IM and promotes a back-up pathway for the cardiolipin synthesis in mitochondria. Thus, porin has roles more than the metabolite transport in the protein and lipid transport into and within mitochondria, which is likely conserved from yeast to human.

scholarly journals Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression of growth-related genes and liver size in adult male sheep

2007 ◽  
Vol 192 (1) ◽  
pp. 87-97 ◽  
Author(s):  
M A Hyatt ◽  
G S Gopalakrishnan ◽  
J Bispham ◽  
S Gentili ◽  
I C McMillen ◽  
...  
Keyword(s):  
Adult Male ◽  
Control Diet ◽  
Mitochondrial Protein ◽  
Live Weight ◽  
Anion Channel ◽  
Cytokine Signaling ◽  
Nutrient Restriction ◽  
Voltage Dependent Anion Channel ◽  
Liver Size ◽  
Male Sheep

The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were sampled. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.

scholarly journals Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep

2003 ◽  
Vol 90 (2) ◽  
pp. 323-328 ◽  
Author(s):  
A. Mostyn ◽  
V. Wilson ◽  
J. Dandrea ◽  
D. P. Yakubu ◽  
H. Budge ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Marked Change ◽  
Anion Channel ◽  
Protein Abundance ◽  
Voltage Dependent Anion Channel ◽  
Maternal Undernutrition ◽  
Brown Adipose ◽  
Near Term

The present study examined the ontogeny of mitochondrial protein abundance in adipose tissue and lungs over the first month of life in the sheep and the extent to which this may be altered by maternal undernutrition during the final month of gestation. The ontogeny of uncoupling protein (UCP), voltage-dependent anion channel (VDAC) and cytochrome c abundance were determined in adipose tissue and lungs sampled from near-term fetuses and young sheep aged 4 h, 1, 7 and 30 d. In adipose tissue, the abundance of UCP1, VDAC and cytochrome c all peaked at 1 d of age and then decreased by 30 d of age, at which stage the brown adipose tissue-specific UCP1 was no longer detectable but UCP2 was clearly abundant. For the lungs, however, UCP2 and VDAC abundance both peaked 7 d after birth and then decreased by 30 d of age. During postnatal development, therefore, a marked change in mitochondrial protein abundance occurs within both adipose tissue and lungs. Maternal nutrient restriction had no effect on lamb growth or tissue weights at 30 d of age but was associated with increased abundance of UCP2 and VDAC but not cytochrome c in both adipose tissue and lungs. These mitochondrial adaptations within both adipose tissue and the lungs of offspring born to previously nutrient-restricted mothers may compromise adipose tissue and lung function during periods of environmental stress.

scholarly journals Timing of nutrient restriction and programming of fetal adipose tissue development

2004 ◽  
Vol 63 (3) ◽  
pp. 397-403 ◽  
Author(s):  
Michael E. Symonds ◽  
Sarah Pearce ◽  
Jayson Bispham ◽  
David S. Gardner ◽  
Terence Stephenson
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Tissue Growth ◽  
Fat Deposition ◽  
Late Gestation ◽  
Nutrient Restriction ◽  
Adult Obesity ◽  
Uncoupling Protein 1 ◽  
Voltage Dependent Anion Channel ◽  
Brown Adipose

It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.

scholarly journals Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring

2009 ◽  
Vol 297 (5) ◽  
pp. F1199-F1207 ◽  
Author(s):  
Don Sharkey ◽  
David S. Gardner ◽  
Michael E. Symonds ◽  
Helen Budge
Keyword(s):  
Kidney Disease ◽  
Inflammatory Response ◽  
Early Onset ◽  
Kidney Development ◽  
Uncoupling Protein ◽  
Innate Immune ◽  
Nutrient Restriction ◽  
Fetal Kidney ◽  
Tubular Atrophy ◽  
Pregnant Sheep

Obesity is an independent risk factor for developing chronic kidney disease. Toll-like receptor 4 (TLR4), interleukin (IL)-18, and uncoupling protein 2 (UCP2) are important components of the innate immune system mediating inflammatory renal damage. Early to midgestation maternal nutrient restriction appears to protect the kidney from the deleterious effects of early onset obesity, although the mechanisms remain unclear. We examined the combined effects of gestational maternal nutrient restriction during early fetal kidney development and early onset obesity on the renal innate immune response in offspring. Pregnant sheep were randomly assigned to a normal (control, 100%) or nutrient-restricted (NR, 50%) diet from days 30 to 80 gestation and 100% thereafter. Offspring were killed humanely at 7 days or, following rearing in an obesogenic environment, at 1 yr of age, and renal tissues were collected. IL-18 and TLR4 expression were strongly correlated irrespective of intervention. Seven-day NR offspring had significantly lower relative renal mass and IL-18 mRNA expression. At 1 yr of age, obesity resulted in increased mRNA abundance of TLR4, IL-18, and UCP2, coupled with tubular atrophy and greater immunohistological staining of glomerular IL-6 and medullary tumor necrosis factor (TNF)-α. NR obese offspring had a marked reduction of TLR4 abundance and renal IL-6 staining. In conclusion, maternal nutrient restriction during early fetal kidney development attenuates the effects of early onset obesity-related nephropathy, in part, through the downregulation of the innate inflammatory response. A better understanding of maternal nutrition and the in utero nutritional environment may offer therapeutic strategies aimed at reducing the burden of later kidney disease.

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