Increase In Mitochondrial Volume Research Articles

Mammals to membranes: A reductionist story.

This is the story of a series of reductionist studies that started with an attempt to explain what underpins the high-level of aerobic metabolism in mammals (i.e. associated with the evolution of endothermy) and almost forty years later had led to investigations into the role of membrane lipids in determining metabolism. Initial studies showed that the increase in aerobic metabolism in mammals was driven by a combination of increases in mitochondrial volume and membrane densities, organ size and changes in the molecular activity of enzymes. The increase in the capacity to produce energy was matched by an increase in energy use, notably driven by increases in H+, Na+ and K+ fluxes. In the case of increased Na+ flux, it was found this was matched by increases in Na+-dependent metabolism at the tissue level and increases in enzyme activity at a cellular level but not by an increase in the number of sodium pumps. To maintain Na+ gradient across cell membranes, increased Na+ flux is not controlled by an increase in sodium pump number but rather by an increase in sodium pump molecular activity (i.e. an increase the substrate turnover rate of each sodium pump) in tissues of endotherms. This increase in molecular activity is coupled to an increase in the level of highly unsaturated polyunsaturated fatty acids (PUFA) in membranes, a mechanism similar to that used by ectotherms to ameliorate decreasing activities of metabolic processes in the cold. Determination of how changes in membrane fatty acid composition can change the activities of proteins in membranes will be the next step in this story.

Building blocks are synthesized on demand during the yeast cell cycle

For cells to replicate, a sufficient supply of biosynthetic precursors is needed, necessitating the concerted action of metabolism and protein synthesis during progressive phases of cell division. A global understanding of which biosynthetic processes are involved and how they are temporally regulated during replication is, however, currently lacking. Here, quantitative multiomics analysis is used to generate a holistic view of the eukaryal cell cycle, using the budding yeast Saccharomyces cerevisiae Protein synthesis and central carbon pathways such as glycolysis and amino acid metabolism are shown to synchronize their respective abundance profiles with division, with pathway-specific changes in metabolite abundance also being reflected by a relative increase in mitochondrial volume, as shown by quantitative fluorescence microscopy. These results show biosynthetic precursor production to be temporally regulated to meet phase-specific demands of eukaryal cell division.

K+ influx triggers slow K+/H+ exchange detected by biphasic changes in matrix pH in Guinea pig cardiomyocyte mitochondria

Recent findings in cell models supports the importance of cation homeostasis by a K+/H+ exchanger (KHE) encoded by the gene LETM1, although LETM1 may also encode Ca2+/H+ exchange and or Na+/H+ exchanger (mNCE). In mitochondria, K+ influx occurs through K+ channels sensitive to Ca2+, Na+, low ATP, and other ligands. K+ influx promotes mitochondrial (m) swelling and contributes to regulation of mitochondrial respiration, membrane potential (mMP) and redox signaling. The influx of mK+ requires a mK+ efflux mechanism (mK+ cycle) paired with H+ influx, which in turn would affect mitochondrial bioenergetics, e.g. respiration, ADP phosphorylation, and mMP due effectively to a “proton leak”. We have previously reported that increased cytosolic and mCa2+ stimulate small and large Ca2+‐sensitive mK+ channels to permit mK+ influx. Cytosolic and mCa2+ increase during ischemia or hypoxia in association with an increase in mitochondrial volume so a high mK+ concentration may be a parallel effect of mCa2+ loading. Experimental conditions that modulate mKHE activity in mammalian cardiac tissue and its consequences have not been examined. Our aim was to provide evidence of mKHE activity in mitochondria isolated from Guinea pig cardiac cell mitochondria and to better understand the circumstances and kinetics of mKHE activity. We proposed that the subsequent efflux of mK+ via mKHE would re‐establish mK+ homeostasis but also provide a “H+ leak” thereby affecting bioenergetics activity. We reasoned that mKHE becomes active once K+ has accumulated in the matrix and that K+ efflux is linked to H+ influx as a marker of mKHE activity. mKHE might be affected by extra‐matrix pH (pHm) as it can change the trans‐membrane pH gradient. To test these ideas, we first added CGP37157 to the mitochondrial buffer to inhibit mNCE. Then we added 25 nM valinomycin, a K+ ionophore, and measured the time‐dependent changes in matrix pHm, using the fluorescent probe BCECF‐AM. We found that across the three extra‐matrix pHs of 6.9, 7.15, and 7.6, matrix pHm transiently increased over approximately 100 s and then transiently decreased over the next 100 s with a slower decline over 20 min. The initial increase in pHm may reflect enhanced proton pumping by respiratory complexes and the secondary decrease in pHm may reflect H+ influx in exchange for K+ efflux, via mKHE. When 500 μM quinine was given before valinomycin to attenuate mKHE, we found that the peak increase in pHm (first phase) occurred later and the subsequent decrease in pHm (second phase) also occurred later by 100 s and was slower to fall over 20 min. The changes to pHm in the presence of quinine provide evidence that the delay in pHm changes were due to block of mKHE by quinine. Interestingly the biphasic effects of valinomycin and quinine on pHm did not appear to be dependent on the extra‐matrix pH values of 6.9, 7.15, 7.6. Additional studies will determine concomitant effects of these protocols on respiration, ADP phosphorylation, mMP, and mitochondrial volume.Support or Funding InformationVA Merit BX‐002539‐01 and NIH T35 HL072483This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MITOCHONDRIAL MEMBRANE POTENTIAL, MORPHOLOGY AND ATP PRODUCTION IN MAMMALIAN CELLS EXPOSED TO X-RAYS.

This study aimed to reveal the effect of X-irradiation on mitochondrial function in terms of mitochondrial membrane potential (ΔΨm) and ATP productivity. At the cellular level, ΔΨm was quantified using JC-1, a mitochondrial probe that emits red or green fluorescence at high or low ΔΨm sites, respectively. The fluorescence area was quantified for both colors together relative to the whole-cell area of the same cell. The fluorescence areas versus whole-cell areas varied widely among the irradiated cells depending on the X-ray doses received (6 and 10 Gy) and incubation time, although the relative red area to total mitochondrial area was rather constant. Average ATP concentrations temporarily increased and showed a maximum at 48 h after irradiation for largely G1-arrested cells. These results indicate that an increase of mitochondrial volume per cell, not simply an increase in their active sites, is induced by irradiation, resulting in enhanced ATP production.

Ketogenic diet increases mitochondria volume in the liver and skeletal muscle without altering oxidative stress markers in rats

Ketogenic diets (KD) consist of high fat, moderate protein and low carbohydrates. Studies have suggested that KD may influence oxidative stress by affecting mitochondrial quantity and/or quality, and perhaps lengthen lifespan. Therefore, we determined the effects of KD on multi-organ mitochondria volume and oxidative stress markers in rats. Ten month-old male Fisher 344 rats (n = 8 per group) were provided with one of two isocaloric diets: standard chow (SC) or KD. Rats were euthanized if: a) vitality scores exceeded a score of 16, b) rapid weight loss, or c) veterinarian deemed euthanasia necessary. The median lifespan of rats was higher in KD (762 days) compared to SC (624 days). Citrate synthase activity (i.e. estimate of mitochondria volume) was higher in the liver (p = 0.034) and gastrocnemius (p = 0.041) of KD compared to SC. Liver superoxide dismutase 1 and catalase antioxidant protein levels were higher in KD, albeit not significant (p = 0.094 and p = 0.062, respectively). No significant differences in protein levels of other antioxidants or markers of lipid and protein oxidative damage were observed in either the gastrocnemius, liver, or brain. In summary, KD increased mitochondria volume in liver and gastrocnemius and median lifespan in rats. Additionally, our data show that the increase in mitochondrial volume occurred without changes in oxidative damage or antioxidant protein levels in the gastrocnemius, liver, or brain.

The effects of dietary β-guanidinopropionic acid on growth and muscle fiber development in juvenile red porgy, Pagrus pagrus.

β-guanidinopropionic acid (β-GPA) has been used in mammalian models to reduce intracellular phosphocreatine (PCr) concentration, which in turn lowers the energetic state of cells. This leads to changes in signaling pathways that attempt to re-establish energetic homeostasis. Changes in those pathways elicit effects similar to those of exercise such as changes in body and muscle growth, metabolism, endurance and health. Generally, exercise effects are beneficial to fish health and aquaculture, but inducing exercise in fishes can be impractical. Therefore, this study evaluated the potential use of supplemental β-GPA to induce exercise-like effects in a rapidly growing juvenile teleost, the red porgy (Pagrus pagrus). We demonstrate for the first time that β-GPA can be transported into teleost muscle fibers and is phosphorylated, and that this perturbs the intracellular energetic state of the cells, although to a lesser degree than typically seen in mammals. β-GPA did not affect whole animal growth, nor did it influence skeletal muscle fiber size or myonuclear recruitment. There was, however, an increase in mitochondrial volume within myofibers in treated fish. GC/MS metabolomic analysis revealed shifts in amino acid composition of the musculature, putatively reflecting increases in connective tissue and decreases in protein synthesis that are associated with β-GPA treatment. These results suggest that β-GPA modestly affects fish muscle in a manner similar to that observed in mammals, and that β-GPA may have application to aquaculture by providing a more practical means of generating some of the beneficial effects of exercise in fishes.

Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion.

Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In β-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in β-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells. CgA deficiency in Chga-KO islets leads to compensatory overexpression of chromogranin B, secretogranin II, SNARE proteins and insulin genes, as well as increased insulin protein content. Ultrastructural studies of pancreatic islets revealed that Chga-KO β-cells contain fewer immature secretory granules than wild-type (WT) control but increased numbers of mature secretory granules and plasma membrane-docked vesicles. Compared to WT control, CgA-deficient β-cells exhibited increases in mitochondrial volume, numerical densities and fusion, as well as increased expression of nuclear encoded genes (Ndufa9, Ndufs8, Cyc1 and Atp5o). These changes in secretory vesicles and the mitochondria likely contribute to the increased glucose-stimulated insulin secretion observed in Chga-KO mice. We conclude that CgA is an important regulator for coordination of mitochondrial dynamics, secretory vesicular quanta and GSIS for optimal secretory functioning of β-cells, suggesting a strong, CgA-dependent positive link between mitochondrial fusion and GSIS.

Paclitaxel-induced increase in mitochondrial volume mediates dysregulation of intracellular Ca2+ in putative nociceptive glabrous skin neurons from the rat

We have recently demonstrated that in a rat model of chemotherapy-induced peripheral neuropathy (CIPN), there is a significant decrease in the duration of the depolarization-evoked Ca2+ transient in small diameter, IB4+, and capsaicin-responsive neurons innervating the glabrous skin of the hindpaw. This change was specific to the transient duration and significantly smaller if not undetectable in neurons innervating the dorsal skin of the hindpaw or the skin of the inner thigh. Given the importance of mitochondria in intracellular Ca2+ regulation and the findings of chemotherapy-associated increase in mitotoxicity along the sensory neuron axons, we hypothesized that CIPN is due to both increases and decreases in mitochondria function, with changes manifest in distinct subpopulations of afferents. To begin to test this hypothesis, we used confocal microscopy and Ca2+ imaging in combination with pharmacological manipulations to study paclitaxel-induced changes in retrograde tracer-labeled neurons from naïve, vehicle-treated, and paclitaxel-treated rats. Paclitaxel treatment was not associated with decreased mitochondrial membrane potential or increased superoxide levels in the somata of putative nociceptive glabrous skin neurons. However, it was associated with significant increases in the relative contribution of mitochondria to the control of the evoked Ca2+ transient duration in putative nociceptive glabrous skin neurons, as well as increases in mitotracker and Tom20 staining which reflected an increase in mitochondrial volume. Furthermore, the relative contribution of the sarco-endoplasmic reticulum Ca2+ ATPase to the regulation of the duration of the depolarization evoked Ca2+ transient was also increased in this subpopulation of neurons from paclitaxel treated rats. Our results indicate that the paclitaxel-induced decrease in the duration of the evoked Ca2+ transient is due to both direct and indirect influences of mitochondria. It remains to be determined if and how these changes contribute to the manifestation of CIPN.

LETM1 in mitochondrial cation transport.

LETM1 in mitochondrial cation transport.

Relationship Between Mitochondrial Matrix Volume and Cellular Volume in Response to Stress and the Role of ATP-Sensitive Potassium Channel

Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI) ± DZX ± 5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI + DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI + DZX + 5HD; P<0.001 CPG+DZX versus CPG + DZX + 5HD). Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.

A novel Mito‐Timer reporter gene for measurement of mitochondrial quantity and quality in vivo

Mitochondrial dysfunction plays an important role in many diseases, but there is no satisfactory method to assess mitochondrial quantity and quality in vivo. Here we engineered a novel pMito‐Timer reporter gene from the existing pTimer‐1 reporter gene. pMito‐Timer encodes a mitochondria‐targeted green fluorescent protein (GFP) when newly synthesized, which shifts irreversibly to red fluorescence (DsRed) when oxidized. Confocal microscopy confirmed that Mito‐Timer targets to mitochondria in cultured mouse myoblasts, Drosophila heart and indirect flight muscles, and adult mouse skeletal muscle. Ratiometric algorithm showed that conditions that cause mitochondrial stress lead to a significant fluorescence shift toward DsRed with a significant increase of DsRed puncta. Somatic gene transfer in adult skeletal muscle in mice showed that high‐fat diet induces the same changes, which could be completely ameliorated by exercise training. Exercise training also results in increases in mitochondrial volume that could be quantified. Therefore, pMito‐Timer can be used to report mitochondrial health under both normal and pathological conditions and will provide a valuable tool to multiple disciplines investigating the role of the mitochondria in disease.

Inverse regulation of the cytosolic Ca²⁺ buffer parvalbumin and mitochondrial volume in muscle cells via SIRT1/PGC-1α axis.

Skeletal muscles show a high plasticity to cope with various physiological demands. Different muscle types can be distinguished by the force, endurance, contraction/relaxation kinetics (fast-twitch vs. slow-twitch muscles), oxidative/glycolytic capacity, and also with respect to Ca2+-signaling components. Changes in Ca2+ signaling and associated Ca2+-dependent processes are thought to underlie the high adaptive capacity of muscle fibers. Here we investigated the consequences and the involved mechanisms caused by the ectopic expression of the Ca2+-binding protein parvalbumin (PV) in C2C12 myotubes in vitro, and conversely, the effects caused by its absence in in fast-twitch muscles of parvalbumin null-mutant (PV−/−) mice in vivo. The absence of PV in fast-twitch muscle tibialis anterior (TA) resulted in an increase in the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and of its positive regulator, the deacetylase sirtuin 1 (SIRT1). TA muscles from PV−/− mice also have an increased mitochondrial volume. Mild ionophore treatment of control (PV-devoid) C2C12 myotubes causing a moderate elevation in [Ca2+]c resulted in an increase in mitochondrial volume, together with elevated PGC-1α and SIRT1 expression levels, whilst it increased PV expression levels in myotubes stably transfected with PV. In PV-expressing myotubes the mitochondrial volume, PGC-1α and SIRT1 were significantly lower than in control C2C12 myotubes already at basal conditions and application of ionophore had no effect on either one. SIRT1 activation causes a down-regulation of PV in transfected myotubes, whilst SIRT1 inhibition has the opposite effect. We conclude that PV expression and mitochondrial volume in muscle cells are inversely regulated via a SIRT1/PGC-1α signaling axis.

Mitochondrial morphology and dynamics in hepatocytes from normal and ethanol-fed rats

Mitochondrial structure and function are central to cell physiology and are mutually interdependent. Mitochondria represent a primary target of the alcohol-induced tissue injury, particularly in the liver, where the metabolic effects of ethanol are predominant. However, the effect of ethanol on hepatic mitochondrial morphology and dynamics remain to be established. In the present work, we employed the organelle-targeted photoactivatable fluorescent protein technology and electron microscopy to study hepatic mitochondrial structure and dynamics. Hepatocytes in perfused liver as well as in primary cultures showed mostly discrete globular or short tubular mitochondria. The mitochondria showed few fusion events and little movement activity. By contrast, human hepatoma (HepG2)-derived VL-17A cells, expressing the major hepatic ethanol metabolizing enzymes, alcohol dehydrogenase and cytochrome P450 2E1, have elongated and interconnected mitochondria showing matrix continuity and many fusion events. Hepatocytes isolated from chronically ethanol-fed rats showed some increase in mitochondrial volume and exhibited a substantial suppression of mitochondrial dynamics. In VL-17A cells, prolonged ethanol exposure also caused decreased mitochondrial continuity and dynamics. Collectively, these results indicate that mitochondria in normal hepatocytes show relatively slow dynamics, which is very sensitive to suppression by ethanol exposure.

Should Willy Wonka have been a sports nutritionist?

Should Willy Wonka have been a sports nutritionist?

A needle in a haystack:focus on “Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart”

diabetes mellitus is increasingly common throughout the world, due to both an increase in incidence and to decreased mortality of those with diabetes. Unfortunately, diabetes more than doubles the risk of cardiovascular disease in adults, and it even causes its own peculiar form of “diabetic”

Do mitochondria in Dendrobium petal mesophyll cells form vacuole-like vesicles?

Using transmission electron microscopy, we investigated the ultrastructure of mitochondria in petal mesophyll cells of the orchid Dendrobium cv. Lucky Duan, from the time of floral opening to visible petal senescence. Cells close to the vascular bundle contained many mitochondria, some of which showed internal degeneration. This inner mitochondrial breakdown was accompanied by an eightfold increase in mitochondrial volume. Small electron-dense granules (approximately 0.04 mum in diameter) at the periphery of the mitochondrial matrix remained. These granules were used as an indicator of still later stages of mitochondrial development in these cells. The apparent final stage of mitochondrial degeneration was a single-membrane-bound vesicle, resembling a vacuole. No evidence was found for the idea that mitochondria became transferred (intact or degenerated) into a lytic vacuole. Taken together, the data suggest the hypotheses that (a) mitochondria in cells close to the vascular bundle in petals of open Dendrobium cv. Lucky Duan flowers undergo large-scale internal degeneration and that (b) such degenerating mitochondria form vacuole-like vesicles.

Increased Potassium Conductance of Brain Mitochondria Induces Resistance to Permeability Transition by Enhancing Matrix Volume

Modulation of K(+) conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood, but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study K(+) channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca(2+) and mitochondrial respiration provided a quantitative assay for mPT sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling induced by increased K(+) or H(+) conductance had opposite effects on mPT sensitivity. Protonophores dose-dependently decreased CRC, demonstrating that so-called mild uncoupling was not beneficial per se. The putative mitoK(ATP) channel opener diazoxide did not mimic the effect of valinomycin. An alkaline matrix pH was required for mitochondria to retain calcium, but increased K(+) conductance did not result in augmented DeltapH. The beneficial effect of valinomycin on CRC was not mediated by H(2)O(2)-induced protein kinase Cepsilon activation. Rather, increased K(+) conductance reduced H(2)O(2) generation during calcium infusion. Lowering the osmolarity of the buffer induced an increase in mitochondrial volume and improved CRC similar to valinomycin without inducing uncoupling or otherwise affecting respiration. We propose that increased potassium conductance in brain mitochondria may cause a direct physiological effect on matrix volume inducing resistance to pathological calcium challenges.

Acute and chronic contractile activity-induced adaptations in muscle and mitochondrial function

Exercise training is a potent stimulus for favourable phenotypic adaptations in muscle, including the induction of mitochondrial biogenesis. Although the occurrence of organelle expansion in response to chronic muscle use is accepted, the cellular events governing this remodeling are undefined. Thus, the purpose of this dissertation was to examine the acute and chronic contractile activity-induced adaptations in skeletal muscle and mitochondrial function in young and old animals. The intracellular signals associated with contractile activity are important for the induction of downstream phenotypic plasticity. In study 1, we investigated the influence of muscle oxygen consumption and reactive oxygen species (ROS) production on kinase signaling. The results demonstrate that mitochondrial content influenced the rate of ROS production in resting muscle. Furthermore, several protein kinases were differentially sensitive to increments in oxygen consumption, and this sensitivity was also related to the muscle mitochondrial volume. In study 2, we further explored the effect of mitochondrial content on the acute contraction-induced kinase signaling in skeletal muscle. We found that mitochondrial content was inversely related to kinase activation in resting skeletal muscle. Moreover, training-induced increases in mitochondrial volume were associated with an attenuated adaptive signaling response subsequent to a single bout of contractions, suggesting a mitochondrially mediated mechanism regulating training-elicited muscle remodeling. The aim of study 3 was to examine the effect of age on the acute exercise-induced signaling response. Skeletal muscle from old animals exhibited pathophysiological properties, including reduced force production, fatigue resistance, mitochondrial content, and ATP-synthesizing ability, all characteristic of aging-associated sarcopenia. This condition was correlated with an attenuated signaling response to acute exercise, which was dependent on muscle mitochondrial content. Study 4 assessed the adaptive plasticity of mitochondria in young and old animals after chronic muscle use. We found that the mitochondria from aged animals were able to adapt favourably to a period of chronic contractile activity, despite an attenuated signaling response after each individual bout of exercise. However, the adaptive plasticity of aged animals was lower than that observed in young animals. These findings underscore the importance of daily physical activity in the maintenance and improvement of health for individuals of all ages.

Python model of physiological and pathological hypertrophy

As an integrative response to the prolonged metabolic demands of digestion, Burmese python (Python molurus) experience rapid growth of their heart. Within 3 days after feeding, pythons have experienced a 40% increase in cardiac mass. Deemed a physiological response to increase cardiovascular performance, the python's cardiac hypertrophy is characterized by an increase in mitochondrial volume and is sensitive to meal size and meal composition. Given that human heart disease is characterized by pathological cardiac hypertrophy, we explored whether we could induce pathological cardiac hypertrophy for the Burmese python using a modified version of transverse aortic constriction. We completely ligated the python's left aortic arch, thereby forcing all systemic blood flow into the right aortic arch and hence generating chronic ventricular pressure overload. Pythons suffered no ill effects from the ligation of their left systemic artery and were able to maintain adequate blood flow through the dorsal aorta. Preliminary examination revealed that ligation of the left systemic artery for 10 ‐ 200 days resulted in a 25% increase in ventricular mass. In addition, the ventricles of these snakes possessed a greater amount of fibrous tissue, a feature characteristic of pathological hypertrophy. We propose the python as a very attractive model to explore the underlying mechanisms of physiological and pathological cardiac hypertrophy. Supported by NSF IOS‐0466139 to SMS.

Cadmium Induced Changes in Metabolic Function of Mitochondrial Isolated from Potato Tissue (Solanum tuberosum L.)

Problem statement: Cadmium is highly toxic at low concentrations, but the mechanism of its toxicity is still not understood particularly at the cellular and subcellular level. Approach: In this study we examined the effects of cadmium on the oxidophosphorylation properties of mitochondria isolated from potatoes. Results: Cadmium strongly disturbed the respiratory metabolism of mitochondria isolated especially in the transfer of electrons by cyanide pathway. Meanwhile, cadmium altered the composition of lipid fatty acids polar while inhibiting catalase activity, a key enzyme in the detoxification (antioxidant) process. In addition, cadmium caused an increase in mitochondrial volume associated with strong inhibition of ATPase activity, which could be explained by a transport of the potassium ion stimulation at the origin of the massive influx of H+ by antiport through the K+/H+ leading to a decoupling (cut) of mitochondrial oxidative phosphorylation. The swelling of mitochondria was accompanied by the rupture of the mitochondrial outer membrane and thus the release of Cytochrome C, which appears to be the initial phase of apoptosis. Conclusion: Following this study, it appeared that cadmium generates in potato the isolated mitochondria a concentration-dependent oxidative stress.