SEARCH · PubMed Health

Results for “Mitochondrial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2005

Compromised liver mitochondrial function and complex activity in low feed efficient broilers are associated with higher oxidative stress and differential protein expression.

Variations in broiler growth and efficiency have been explained in part by differences in mitochondrial function and biochemistry in broilers. To further our knowledge in this regard, 2 experiments were carried out to determine the relationships of a) mitochondrial function and activities of various electron transport chain (ETC) complexes; b) production of H2O2, a reactive oxygen species (ROS), and its association with protein oxidation; and c) mitochondrial protein expression in liver of a single line male broilers with low or high feed efficiency (FE, n = 5 to 8 per group). Mitochondrial function and complex activities were measured polarographically and spectrophotometrically, respectively. H2O2 was measured fluorimetrically, whereas oxidized protein (carbonyls) and specific mitochondrial proteins were analyzed using Western blots. Mitochondrial function (ETC coupling) and activities of ETC complexes (I, II, III, and IV) were higher in high FE compared with low FE broilers. H2O2 and protein carbonyls were higher in the livers of low FE broilers than in high FE broilers. Whereas the expression of 4 immunoreactive proteins [NAD3 (complex I), subunit VII (complex III), cytochrome c oxidase subunits (COX) II, and COX IVb (complex IV)] were higher in low FE liver mitochondria and 2 proteins [subunit 70 (complex II) and a-ATP synthase (complex V)] were higher in high FE birds, there were no differences between groups in the expression of 18 other mitochondrial proteins. In conclusion, increases in oxidative stress in low FE broilers were caused by or may contribute to differences in mitochondrial function (ETC coupling and complex activities) or the differential expression of steady-state levels of some mitochondrial proteins in the liver. Understanding the role of oxidative stress in Low FE broilers will provide clues in understanding the cellular basis of feed efficiency.

Animal Feed↗

PubMed2002

Impaired mitochondrial function protects against free radical-mediated cell death.

Free radical damage can have fatal consequences. Mitochondria carry out essential cellular functions and produce high levels of reactive oxygen species (ROS). Many agents also generate ROS. Using the yeast Saccharomyces cerevisiae as a eukaryotic model, the role of functional mitochondria in surviving free radical damage was investigated. Respiratory-deficient cells lacking mitochondrial DNA (rho(0)) were up to 100-fold more resistant than isogenic rho(+) cells to killing by ROS generated by the bleomycin-phleomycin family of oxidative agents. Up to approximately 90% of the survivors of high oxidative stress lost mitochondrial function and became "petites." The selective advantage of respiratory deficiency was studied in several strains, including DNA repair-deficient rad52/rad52 and blm5/blm5 diploid strains. These mutant strains are hypersensitive to lethal effects of free radicals and accumulate more DNA damage than related wild-type strains. Losses in mitochondrial function were dose-dependent, and mutational alteration of the RAD52 or BLM5 gene did not affect the resistance of surviving cells lacking mitochondrial function. The results indicate that inactivation of mitochondrial function protects cells against lethal effects of oxygen free radicals.

Antibiotics, Antineoplastic↗

PubMed1998

Mucosal mitochondrial function and antioxidant defences in patients with gastric carcinoma.

BACKGROUND: Cancer cells have alterations in energy metabolism due to defective mitochondrial function. This may be due to generation of excessive free radicals and/or defective antioxidant enzyme systems. The aim of the present study was to assess mitochondrial function and antioxidant defences in the gastric mucosa of patients with gastric carcinoma (CA). METHODS: Gastric mucosal mitochondrial function was assessed by means of the reduction of tetrazolium dye (MTT), and levels of antioxidants such as glutathione S-transferase (GST), catalase, superoxide dismutase (SOD), and thiols were measured in biopsy specimens taken from the tumour mucosa (TM) and tumour-free (TF) mucosa, 2 cm away from the tumour, in 49 patients with gastric CA and compared with that in 54 controls. In a further 10 patients with gastric CA, these studies were done on TM and TF mucosa 2 cm and > or = 5 cm away from the tumour. In 10 patients and 5 controls, specimens were obtained for electron microscopy as well. Helicobacter pylori infection was diagnosed by means of histology. RESULTS: MTT reduction and GST and SOD activities were significantly decreased in TM and TF mucosa in patients with CA compared with controls (P < 0.01). The levels of thiols and catalase activity were significantly increased in CA as compared with controls (P < 0.01). H. pylori positivity did not influence most of these variables but did give significant decrease in MTT reduction in CA (TF) mucosa (P=0.01) and significant increase in thiol levels in CA (TM) mucosa (P=0.04). Electron microscopy showed mitochondrial alterations in tumour cells in all patients and in adjacent mucosa of 10%-50% of the cells. CONCLUSIONS: 1) In gastric CA the cancer mucosal cells and the non-involved cells adjacent to the tumour have defective mitochondrial function, which may be due to altered antioxidant defences and possibly altered free radical formation. 2) Ultrastructural mitochondrial abnormalities are shown to parallel these biochemical abnormalities.

Adult↗

PubMed2006

Preconditioning prevents loss in mitochondrial function and release of cytochrome c during prolonged cardiac ischemia/reperfusion.

Loss in mitochondrial function and induction of mitochondrial-mediated apoptosis occur as a result of cardiac ischemia/reperfusion. Brief and repeated cycles of ischemia/reperfusion, termed ischemic preconditioning, prevent or minimize contractile dysfunction and apoptosis associated with prolonged episodes of cardiac ischemia and reperfusion. The effects of preconditioning on various indices of ischemia/reperfusion-induced alterations in mitochondrial function and structure were therefore explored. Utilizing an in vivo rat model data is provided indicating that preconditioning completely prevents cardiac ischemia/reperfusion-induced: (1) loss in the activity of the redox sensitive Krebs cycle enzyme alpha-ketoglutarate dehydrogenase; (2) declines in NADH-linked ADP-dependent mitochondrial respiration; (3) insertion of the pro-apoptotic Bcl-2 protein Bax into the mitochondrial membrane; and (4) release of cytochrome c into the cytosol. The results of the current study indicate that preconditioning prevents specific alterations in mitochondrial structure and function that are known to impact cellular viability and provide insight into the collective benefits of preconditioning.

Animals↗

PubMed2006

Relationship between insulin sensitivity and in vivo mitochondrial function in skeletal muscle.

Recent data have shown that individuals with low insulin sensitivity (S(I)) also have reduced whole body maximal oxygen uptake. The objectives of this study were to determine 1) whether muscle mitochondrial function was independently related to S(I) after being adjusted for known determinants of S(I) and 2) whether lower S(I) among African-American (AA) vs. Caucasian-American (CA) women was due to lower muscle mitochondrial function among AA women. Subjects were 37 CA and 22 AA premenopausal women (age: 33.6 +/- 6.3 yr). Mitochondrial function [time constant of ADP (ADP(tc))] was assessed during a 90-s unilateral isometric contraction using (31)P magnetic resonance spectroscopy, S(I) with an intravenous glucose tolerance test, body composition by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) with computed tomography. ANOVA was used to compare AA and CA groups, and multiple linear regression modeling was used to identify independent predictors of S(I). Between-race comparisons indicated that muscle oxidative capacity was lower among AAs vs. CAs (ADP(tc): 25.6 +/- 9.8 vs. 21.4 +/- 9.9 s). Multiple linear regression models for the dependent variable S(I) contained 1) VAT and race and 2) VAT, race, and ADP(tc). Significant independent effects for all predictor variables were observed in both the first (r(2) = 0.345) and second (r(2) = 0.410) models. The partial correlation for race was lower in the second model (-0.404 vs. -0.300), suggesting that muscle mitochondrial function contributed to the racial difference in S(I). Lower muscle mitochondrial function among AAs may in part explain lower S(I) among them.

Absorptiometry, Photon↗

PubMed2004

Vitamin E or coenzyme Q10 administration is not fully advantageous for heart mitochondrial function in diabetic goto kakizaki rats.

The heart is one of the organs affected during the later stages of diabetes. Mitochondrial function has already been proposed to be affected during the course of diabetes. Nevertheless, little information is known concerning the impact of antioxidants in heart mitochondria of a milder model for diabetes, such as the Goto-Kakizaki (GK) rat, where mitochondrial function appears ameliorated. The objective of this work was to test if injections of Vitamin E and Coenzyme Q10, alone and in combination, were able to modify mitochondrial performance in the hearts of GK rats. Several aspects of mitochondrial function were measured, such as the respiratory control ratio and the electric potential, as well as the mitochondrial accumulation of Vitamin E and Coenzymes Q9 and Q10. We observed that only Vitamin E appeared to have a positive impact on the mitochondrial phosphorylation efficiency and on mitochondrial performance, namely on the ability to generate the electric transmembrane potential in the presence of supra-physiological calcium concentrations. Vitamin E administration also increased the mitochondrial concentration of Coenzyme Q10. None of the treatments was able to reverse the diabetic phenotype in GK rats. We conclude that in this model of mild hyperglycemia, administration of antioxidants may have a marginal positive impact on mitochondrial function.

Journal Article↗

PubMed2001

Acute valproate-associated microvesicular steatosis: could the [13C]methionine breath test be useful to assess liver mitochondrial function?

Microvesicular steatosis is a potentially severe manifestation of valproic acid hepatotoxicity due to an acquired impairment of mitochondrial function. Tests currently used to investigate mitochondrial fonction are cumbersome and cannot be used routinely. We report on a noninvasive breath test using [13C]methionine for estimation of mitochondrial function in a case of pure severe valproic acid overdose-induced microvesicular changes. The initially abnormal breath test improved together with the recovery of liver failure. In conclusion, this observation suggests that the [13C]methionine breath test may provide a noninvasive estimate of hepatic mitochondrial function in vivo.

Adult↗

PubMedDate not supplied

In situ mitochondrial function in volume overload- and pressure overload-induced cardiac hypertrophy in rats.

OBJECTIVES: Little comparative information is available on mitochondrial function changes during experimentally-induced hypertrophy. Respiratory control mechanisms are not exactly the same in situ and in isolated mitochondria. This study assessed in situ mitochondrial function in two myocardial hypertrophy models. METHODS: Cytochrome aa3 (Cytaa3) and myoglobin (Mb) absorption changes were monitored in isolated rat hearts using dual wavelength spectrophotometry (Cytaa3: 605-630 nm, Mb: 581-592 nm). Hypertrophy was induced by creation of an aortic stenosis or of an aorto-caval fistula. Optical monitoring was performed on diastole-arrested perfused hearts using the sequence O2 perfusion, N2 perfusion during 4 min, and reoxygenation. The plateaus of the Cytaa3 and Mb curves were used to quantify oxidation-reduction and oxygenation levels. Respiratory kinetics were characterized by the slopes of transition phase curves. RESULTS: Myoglobin oxygenation was comparable in the hypertrophied and control hearts. However, Cytaa3 oxidation-reduction levels in the hypertrophied hearts showed a shift towards greater reduction in comparison with the controls (controls: 0.580 +/- 0.008 DO605/DO630 nm, n = 34; fistula: 0.530 +/- 0.023, n = 23; stenosis: 0.522 +/- 0.016, n = 20, p < 0.001). The rate of Cytaa3 reduction and the rate of myoglobin deoxygenation were significantly accelerated (p < 0.005) in the volume overload group (0.507 +/- 0.043, n = 23), whereas the respiratory rate in the pressure overload group (0.389 +/- 0.034, n = 20) was comparable to that in the control hearts (0.358 +/- 0.026 delta DO 605 nm/DO630 nm.min-1, n = 34). CONCLUSION: We found mitochondrial function alterations in both volume overload- and pressure overload-induced cardiac hypertrophy, despite adequate cytosol oxygenation. The patterns of these alterations differed: the redox state showed a shift of similar magnitude toward greater reduction in both models, but the respiratory rate was increased in the volume-overloaded hearts and unchanged in the pressure-overloaded hearts. The modification in the oxidation-reduction state suggested that overload hypertrophy may induce changes in the metabolism of the myocardium, which may, in turn, load to persistent modifications in mitochondrial function. The differences between the two models suggest that adaptation to hypertrophy-inducing events exists at the level of the mitochondrion.

Absorption↗

PubMedDate not supplied

Role of substrates in the regulation of mitochondrial function in situ.

Investigations of mitochondrial oxidative phosphorylation have been mainly carried out in isolated mitochondria, where the experimental conditions can be precisely set. However, in intact living systems oxidative phosphorylation takes place in a complex environment, whose experimental dissection is a major challenge. It has long been recognized that the efficiency of oxidative phosphorylation depends on the nature of the respiratory substrates, which feed electrons to the respiratory chain at different levels. Yet, the role of substrates in determining mitochondrial function and their response to energetic stress has been largely overlooked. Here we review recent work showing that the nature of the energetic substrates profoundly affects the mitochondrial responses to manipulations of pathophysiological relevance, such as uncoupling and opening of the permeability transition pore (PTP). Uncoupling of intact hepatocytes caused very different metabolic effects depending on whether carbohydrates or lipids were the energy source. With dihydroxyacetone as the substrate dinitrophenol caused a collapse of the mitochondrial membrane potential and of the ATP/ADP ratio, while the respiratory rate was increased only transiently. With octanoate as the substrate, on the other hand, dinitrophenol caused a dramatic stimulation of the respiratory rate, while the mitochondrial membrane potential and ATP/ADP ratio were affected only marginally. We then review results indicating that the activity of complex I directly regulates the PTP, a finding that emphasizes the importance of the respiratory substrates in PTP regulation.

Adenosine Triphosphate↗

PubMed2003

Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly.

BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.

Adenosine Diphosphate↗

PubMed2004

Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients.

Several lines of evidence suggest an impairment of mitochondrial function in the brain of patients with Parkinson's disease (PD). However, the presence of a detectable mitochondrial defect in extracerebral tissue of these patients remains a matter of dispute. Therefore, we investigated mitochondrial function in fibroblasts of 18 PD patients applying biochemical micromethods. Putative beneficial effects of coenzyme Q(10) (CoQ(10)), a potent antioxidant, on the mitochondrial function of skin fibroblast cultures were evaluated. Applying inhibitor titrations of the mitochondrial respiration to calculate flux control coefficients of respiratory chain complexes I and IV, we observed deficiencies of both complexes in cultivated skin fibroblasts of PD patients. Cultivation of fibroblasts in the presence of 5 microM CoQ(10) restored the activity of impaired respiratory chain complexes in the fibroblast cultures of 9 out of 18 PD patients. Our data support the presence of a generalised mitochondrial defect in at least a subgroup of patients with PD that can be partially ameliorated in vitro by coenzyme Q(10) treatment.

Adenosine Diphosphate↗

PubMed2001

Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis.

To determine the importance of mitochondrial reactive oxygen species toxicity in aging and senescence, we analyzed changes in mitochondrial function with age in mice with partial or complete deficiencies in the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD). Liver mitochondria from homozygous mutant mice, with a complete deficiency in MnSOD, exhibited substantial respiration inhibition and marked sensitization of the mitochondrial permeability transition pore. Mitochondria from heterozygous mice, with a partial deficiency in MnSOD, showed evidence of increased proton leak, inhibition of respiration, and early and rapid accumulation of mitochondrial oxidative damage. Furthermore, chronic oxidative stress in the heterozygous mice resulted in an increased sensitization of the mitochondrial permeability transition pore and the premature induction of apoptosis, which presumably eliminates the cells with damaged mitochondria. Mice with normal MnSOD levels show the same age-related mitochondrial decline as the heterozygotes but occurring later in life. The premature decline in mitochondrial function in the heterozygote was associated with the compensatory up-regulation of oxidative phosphorylation enzyme activity. Thus mitochondrial reactive oxygen species production, oxidative stress, functional decline, and the initiation of apoptosis appear to be central components of the aging process.

Aging↗

PubMed1999

Evidence of mitochondrial dysfunction in broilers with pulmonary hypertension syndrome (Ascites): effect of t-butyl hydroperoxide on hepatic mitochondrial function, glutathione, and related thiols.

The purpose of this study was to assess mitochondrial function and glutathione (a mitochondrial antioxidant) in response to oxidative stress in mitochondria in vitro obtained from broilers with and without pulmonary hypertension syndrome (PHS). Liver mitochondria from Control and PHS broilers were incubated with 0, 1, and 5-mM tertiary-butyl hydroperoxide (tBH). Indices of mitochondrial function [the respiratory control ratio (RCR) and the adenosine diphosphate to oxygen ratio (ADP:O)], and levels of mitochondrial and extra-mitochondrial reduced (GSH) and oxidized (GSSG) glutathione, cysteine, cystine, glutamate and cysteinyl-glycine were determined following tBH treatment. Lower RCR and ADP:O values were observed in PHS mitochondria than in controls. Whereas control mitochondria remained coupled (RCR > 2.0), only 3 PHS preparations remained coupled after 60 min of incubation with 5 mM tBH, indicating a greater susceptibility to oxidative stress in PHS mitochondria. The lower RCR in PHS mitochondria was due to increased oxygen consumption during State IV respiration. Oxidative stress following tBH treatment (decreased GSH and increased GSSG) was observed, but there were no differences in GSH or GSSG between control and PHS mitochondria. The PHS mitochondria did exhibit elevated mitochondrial and extramitochondrial cystine than controls, however. The results indicate that PHS mitochondria do not lack antioxidant protection from GSH, but lower RCR and ADP:O ratios in PHS mitochondria indicate a dysfunction that may contribute to the pathophysiology of this metabolic disease in broilers.

Adenosine Diphosphate↗

PubMed2004

Altered mitochondrial function and cholesterol synthesis influences protein synthesis in extended HepG2 spheroid cultures.

Cultures of hepatocytes and HepG2 cells provide useful in vitro models of liver specific function. In this study, we investigated metabolic and biosynthetic function in 3-D HepG2 spheroid cultures, in particular to characterise changes on prolonged culture. We show that HepG2 cells cultured in spheroids demonstrate a reduction in mitochondrial membrane potential and respiration following 10 days of culture. This coincides with a modest reduction in glycolysis but an increase in glucose uptake where increased glycogen synthesis occurs at the expense of the intracellular ATP pool. Lowered biosynthesis coincides with and is linked to mitochondrial functional decline since low glucose-adapted spheroids, which exhibit extended mitochondrial function, have stable biosynthetic activity during extended culture although biosynthetic function is lower. This indicates that glucose is required for biosynthetic output but sustained mitochondrial function is required for the maintenance of biosynthetic function. Furthermore, we show that cholesterol synthesis is markedly increased in spheroids cf. monolayer culture and that inhibition of cholesterol synthesis by lovastatin extends mitochondrial and biosynthetic function. Therefore, increased cholesterol synthesis and/or its derivatives contributes to mitochondrial functional decline in extended HepG2 spheroid cultures.

Albumins↗

PubMed1994

Mitochondrial function reflected by the decarboxylation of [13C]ketoisocaproate is impaired in alcoholics.

Mitochondria of patients with alcoholic liver disease exhibit structural abnormalities, and mitochondria isolated from animals exposed to ethanol are functionally deficient when studied in vitro. To assess possible functional consequences of these ethanol-associated alterations in vivo, we measured mitochondrial function in alcoholics noninvasively with a breath test. A mitochondrial function, the decarboxylation of ketoisocaproate (KICA), was assessed by measuring the exhalation of 13CO2 following the administration of 1 mg/kg 2-keto[1-13C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the KICA breath test in 12 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 13CO2 and the fraction of the administered dose decarboxylated in 120 min were both significantly lower in alcoholics than in healthy controls and patients with nonalcoholic liver disease. In alcoholics, KICA decarboxylation was impaired in the presence of normal quantitative liver function tests such as the aminopyrine breath test and galactose elimination capacity, indicating that KICA decarboxylation does not simply reflect a decreased functional hepatic mass. The enrichment of circulating KICA with [13C]KICA was similar in alcoholics and controls, indicating that a decreased bioavailability or an increased dilution of labeled KICA cannot account for the decreased exhalation of 13CO2. It is concluded that mitochondrial function as reflected by KICA decarboxylation is impaired in chronic alcoholics. The functional impairment is specific for ethanol abuse and not a reflection of decreased global hepatic function. KICA decarboxylation could thus be useful as a marker for excessive ethanol consumption.

Adult↗

PubMedDate not supplied

Subcellular heterogeneity of mitochondrial function and dysfunction: evidence obtained by confocal imaging.

Beyond their fundamental role in energy metabolism, mitochondria perform a great variety of other important functions (e.g. in Ca2+ homeostasis, apoptosis, thermogenesis, etc.), thus suggesting their region-specific specializations and intracellular heterogeneity. Although mitochondrial functional heterogeneity has been demonstrated for several cell types, its origin and role under physiological and, in particular, pathophysiological conditions, where the extent of heterogeneity may significantly increase, remain to be elucidated. The present work thus investigated the static and dynamic heterogeneity of mitochondria and mitochondrial function in various cell types in which mitochondria may cope with specific functions including cardiomyocytes, hepatocytes and some cultured carcinoma cells. Modern confocal and two-photon fluorescent microscopy was used for the investigation and direct imaging of region-specific mitochondrial function and heterogeneity. Analysis of the autofluorescence of mitochondrial flavoproteins in hepatocytes and carcinoma cells permitted significant intracellular heterogeneity of mitochondrial redox state to be demonstrated. Comparative homogeneity and clear colocalization of mitochondrial flavoproteins, membrane potential and calcium-sensitive probes were observed in both isolated cardiomyocytes and permeabilized myocardial fibers. After ischemia reperfusion, however, or under conditions of substrate deprivation, significant heterogeneity of all these parameters was detected. Some methodological issues, mechanistic aspects, possible metabolic consequences of mitochondrial functional heterogeneity and its impact under pathological conditions are discussed.

Animals↗

PubMed2004

Assay of mitochondrial functions by resazurin in vitro.

AIM: To study the mechanism of resazurin as indicator of mitochondrial function and to develop a rapid and sensitive assay for measuring metabolic activity of isolated mitochondria from rat liver in vitro. METHODS: The screening was carried out on 96-well microtitre plates by monitoring fluorescence intensity of resazurin reduced by mitochondria. Experimental conditions were optimized and influences of several inhibitors on mitochondrial function were observed. RESULTS: Fluorescence intensity increased in a linear manner when the mitochondrial protein concentration from 5 to 50 microg protein per well was incubated with resazurin (5 micromol/L) during 230 min period at 37 degrees C. Edetic acid could promote the reduction of resazurin in mitochondria. The fluorescence intensity decreased greatly after pretreatment with NaN3, antimycin A, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), and oligomycin compared with the control. However, the typical complex I inhibitor, rotenone enhanced the fluorescence intensity without mitochondria. CONCLUSION: Using resazurin to determine mitochondrial function is sensitive, inexpensive and could be easily automated for high throughput screening.

Animals↗

PubMed1996

Role of ornithine decarboxylase in enterocyte mitochondrial function and integrity.

We examined the role of ornithine decarboxylase (ODC) and polyamine biosynthesis in regulating mitochondrial function and integrity along the crypt-villus axis in male Sprague-Dawley rats. Isolated villus tip enterocytes from control rats demonstrated a greater cellular capacity for glucose oxidation than crypt enterocytes. Mitochondrial enzyme activities were similar along the crypt-villus axis. The role of ODC was assessed by treating experimental rats with the irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO) for 24 h. Animals receiving DFMO demonstrated a decreased CO2 production from [2-(14)C]pyruvate along the entire crypt-villus axis coupled with an increase in lactate production in the upper cell populations. CO2 production from [14C]glucose and total ATP levels were not affected by DFMO treatment. Ultrastructural examination revealed localized mitochondrial swelling and bursting only in enterocytes corresponding to the population of cells newly emerged from the crypt during DFMO treatment. In DFMO-treated animals, 2 microM spermine completely prevented the structural mitochondrial injury and restored the metabolic crypt-villus gradient. These results suggest that as enterocytes migrate from the crypt up the villus, mitochondrial function increases to handle the increased metabolic demands placed on the cell by nutrient absorption. ODC activity and polyamines are necessary for this increased mitochondrial function and have a role in the maintenance of mitochondrial integrity in maturing enterocytes migrating from the crypt onto the villus.

Animals↗