Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae)

Snakes are interesting examples of overcoming energy metabolism challenges as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption, and protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, and then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria. From isolated mitochondria, we also measured Ca2+ retention capacity and redox status. Mitochondrial respiration rates were maximized after feeding, reaching approximately a 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition (MPT), and no changes in mitochondrial redox state, although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase mitochondrial respiration rates during the postprandial period and quickly improve the mitochondrial bioenergetics capacity without compromising redox balance.

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Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae)

10.1101/2021.07.05.451168 ◽

2021 ◽

Author(s):

Helena R.M. Araujo ◽

Marina Rincon Sartori ◽

Claudia D.C. Navarro ◽

Jose Eduardo de Carvalho ◽

Andre Luis Cruz

Keyword(s):

Redox State ◽

Citrate Synthase ◽

Mitochondrial Permeability Transition ◽

Respiratory Control ◽

Permeability Transition ◽

Mitochondrial Bioenergetics ◽

Retention Capacity ◽

Isolated Mitochondria ◽

Respiration Rates ◽

Boa Constrictor

Snakes are interesting examples of overcoming energy metabolism challenges as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption and, protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria, and from isolated mitochondria, we also measured Ca2+ retention capacity, the release of H2O2, and NAD(P) redox state. Mitochondrial respiration rates were maximized after feeding, reaching until 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition pore (PTP), or redox state of NAD(P), although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase the maintenance costs during the postprandial period and quickly improve the mitochondrial bioenergetics capacity without compromising the redox balance.

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Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0462 ◽

2015 ◽

Vol 40 (6) ◽

pp. 565-574 ◽

Cited By ~ 15

Author(s):

Aline Isabel da Silva ◽

Glauber Ruda Feitoza Braz ◽

Reginaldo Silva-Filho ◽

Anderson Apolonio Pedroza ◽

Diorginis Soares Ferreira ◽

...

Keyword(s):

Skeletal Muscle ◽

Metabolic Diseases ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Wistar Rat ◽

Male Rats ◽

Mitochondrial Activity ◽

Rat Tissues ◽

Transferase Activity ◽

Mitochondrial Bioenergetics

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

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Ageing-induced decrease in cardiac mitochondrial function in healthy rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0422 ◽

2013 ◽

Vol 91 (8) ◽

pp. 593-600 ◽

Cited By ~ 20

Author(s):

Oana M. Duicu ◽

Silvia N. Mirica ◽

Dorina E. Gheorgheosu ◽

Andreea I. Privistirescu ◽

Ovidiu Fira-Mladinescu ◽

...

Keyword(s):

Mitochondrial Function ◽

Complex I ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Heart Mitochondria ◽

Ros Production ◽

Sprague Dawley ◽

Retention Capacity ◽

Mptp Opening ◽

Sprague Dawley Rats

It is widely recognized that mitochondrial dysfunction is a key component of the multifactorial process of ageing. The effects of age on individual components of mitochondrial function vary across species and strains. In this study we investigated the oxygen consumption, the mitochondrial membrane potential (Δψ), the sensitivity of mitochondrial permeability transition pore (mPTP) to calcium overload, and the production of reactive oxygen species (ROS) in heart mitochondria isolated from old compared with adult healthy Sprague–Dawley rats. Respirometry studies and Δψ measurements were performed with an Oxygraph-2k equipped with a tetraphenylphosphonium electrode. ROS production and calcium retention capacity were measured spectrofluorimetrically. Our results show an important decline for all bioenergetic parameters for both complex I and complex II supported-respiration, a decreased Δψ in mitochondria energized with complex I substrates, and an increased mitochondrial ROS production in the old compared with the adult group. Mitochondrial sensitivity to Ca2+-induced mPTP opening was also increased in the old compared with the adult animals. Moreover, the protective effect of cyclosporine A on mPTP opening was significantly reduced in the old group. We conclude that healthy ageing is associated with a decrease in heart mitochondria function in Sprague–Dawley rats.

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Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition

Pharmaceuticals ◽

10.3390/ph14101045 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1045

Author(s):

Ekaterina S. Kharechkina ◽

Anna B. Nikiforova ◽

Konstantin N. Belosludtsev ◽

Tatyana I. Rokitskaya ◽

Yuri N. Antonenko ◽

...

Keyword(s):

Adverse Effects ◽

Oxidative Phosphorylation ◽

Mitochondrial Permeability Transition ◽

Kidney Diseases ◽

Adenine Nucleotides ◽

Permeability Transition ◽

Protective Effects ◽

Retention Capacity ◽

Mptp Opening

Pioglitazone (PIO) is an insulin-sensitizing antidiabetic drug, which normalizes glucose and lipid metabolism but may provoke heart and liver failure and chronic kidney diseases. Both therapeutic and adverse effects of PIO can be accomplished through mitochondrial targets. Here, we explored the capability of PIO to modulate the mitochondrial membrane potential (ΔΨm) and the permeability transition pore (mPTP) opening in different models in vitro. ΔΨm was measured using tetraphenylphosphonium and the fluorescent dye rhodamine 123. The coupling of oxidative phosphorylation was estimated polarographically. The transport of ions and solutes across membranes was registered by potentiometric and spectral techniques. We found that PIO decreased ΔΨm in isolated mitochondria and intact thymocytes and the efficiency of ADP phosphorylation, particularly after the addition of Ca2+. The presence of the cytosolic fraction mitigated mitochondrial depolarization but made it sustained. Carboxyatractyloside diminished the PIO-dependent depolarization. PIO activated proton transport in deenergized mitochondria but not in artificial phospholipid vesicles. PIO had no effect on K+ and Ca2+ inward transport but drastically decreased the mitochondrial Ca2+-retention capacity and protective effects of adenine nucleotides against mPTP opening. Thus, PIO is a mild, partly ATP/ADP-translocase-dependent, uncoupler and a modulator of ATP production and mPTP sensitivity to Ca2+ and adenine nucleotides. These properties contribute to both therapeutic and adverse effects of PIO.

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Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg2+ Ions

The Journal of Cell Biology ◽

10.1083/jcb.143.1.217 ◽

1998 ◽

Vol 143 (1) ◽

pp. 217-224 ◽

Cited By ~ 459

Author(s):

Robert Eskes ◽

Bruno Antonsson ◽

Astrid Osen-Sand ◽

Sylvie Montessuit ◽

Christoph Richter ◽

...

Keyword(s):

Cytochrome C ◽

Cyclosporin A ◽

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Cytochrome C Release ◽

Mitochondrial Permeability ◽

Isolated Mitochondria ◽

Mammalian Homologue

Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A–sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg2+ and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg2+ sensitive but cyclosporin insensitive.

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Protectors of the mitochondrial permeability transition pore activated by iron and doxorubicin

Current Cancer Drug Targets ◽

10.2174/1568009621999210120192558 ◽

2021 ◽

Vol 21 ◽

Author(s):

Tatiana A. Fedotcheva ◽

Nadezhda I. Fedotcheva

Keyword(s):

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Membrane Damage ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Selective Electrode ◽

Mitochondrial Permeability ◽

Isolated Mitochondria ◽

Mptp Opening ◽

Dependent Cell

Aim: The study of action of iron, DOX, and their complex on the mitochondrial permeability transition pore (MPTP) opening and the detection of possible protectors of MPTP in the conditions close to mitochondria-dependent ferroptosis. Background: The toxicity of doxorubicin (DOX) is mainly associated with the free iron accumulation and mitochondrial dysfunction. DOX can provoke ferroptosis, iron-dependent cell death driven by the membrane damage. The mitochondrial permeability transition pore (MPTP) is considered as a common pathway leading to the development of apoptosis, necrosis, and, possibly, ferroptosis. The influence of DOX on the Ca2+ -induced opening of MPTP in the presence of iron has not yet been studied. Objective: The study was conducted on isolated liver and heart mitochondria. MPTP and succinate-ubiquinone oxidoreductase were studied as targets of DOX in mitochondria-dependent ferroptosis. Methods: The study was conducted on isolated mitochondria of the liver and heart. Changes of threshold calcium concentrations required for MPTP opening were measured by a Ca2+ selective electrode, mitochondrial membrane potential was registered by tetraphenylphosphonium (TPP+)-selective electrode, and mitochondrial swelling was recorded as a decrease in absorbance at 540 nm. The activity of succinate dehydrogenase (SDH) was determined by the reduction of the electron acceptor DCPIP. Conclusion: MPTP and the respiratory complex II are identified as the main targets of the iron-dependent action of DOX on the isolated mitochondria. All MPTP protectors tested abolished or weakened the effect of iron and a complex of iron with DOX on Ca2+ -induced MPTP opening, acting in different stages of MPTP activation. These data open new approaches to the modulation of the toxic influence of DOX on mitochondria with the aim to reduce their dysfunction

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Altered skeletal muscle microtubule-mitochondrial VDAC2 binding is related to bioenergetic impairments after paclitaxel but not vinblastine chemotherapies

AJP Cell Physiology ◽

10.1152/ajpcell.00384.2018 ◽

2019 ◽

Vol 316 (3) ◽

pp. C449-C455 ◽

Cited By ~ 4

Author(s):

Sofhia V. Ramos ◽

Meghan C. Hughes ◽

Christopher G. R. Perry

Keyword(s):

Skeletal Muscle ◽

Direct Interaction ◽

Permeability Transition Pore ◽

Anion Channel ◽

Permeability Transition ◽

Mitochondrial Bioenergetics ◽

Voltage Dependent Anion Channel ◽

Retention Capacity ◽

Microtubule Stabilization

Microtubule-targeting chemotherapies are linked to impaired cellular metabolism, which may contribute to skeletal muscle dysfunction. However, the mechanisms by which metabolic homeostasis is perturbed remains unknown. Tubulin, the fundamental unit of microtubules, has been implicated in the regulation of mitochondrial-cytosolic ADP/ATP exchange through its interaction with the outer membrane voltage-dependent anion channel (VDAC). Based on this model, we predicted that disrupting microtubule architecture with the stabilizer paclitaxel and destabilizer vinblastine would impair skeletal muscle mitochondrial bioenergetics. Here, we provide in vitro evidence of a direct interaction between both α-tubulin and βII-tubulin with VDAC2 in untreated single extensor digitorum longus (EDL) fibers. Paclitaxel increased both α- and βII-tubulin-VDAC2 interactions, whereas vinblastine had no effect. Utilizing a permeabilized muscle fiber bundle preparation that retains the cytoskeleton, paclitaxel treatment impaired the ability of ADP to attenuate H2O2 emission, resulting in greater H2O2 emission kinetics. Despite no effect on tubulin-VDAC2 binding, vinblastine still altered mitochondrial bioenergetics through a surprising increase in ADP-stimulated respiration while also impairing ADP suppression of H2O2 and increasing mitochondrial susceptibility to calcium-induced formation of the proapoptotic permeability transition pore. Collectively, these results demonstrate that altering microtubule architecture with chemotherapeutics disrupts mitochondrial bioenergetics in EDL skeletal muscle. Specifically, microtubule stabilization increases H2O2 emission by impairing ADP sensitivity in association with greater tubulin-VDAC binding. In contrast, decreasing microtubule abundance triggers a broad impairment of ADP’s governance of respiration and H2O2 emission as well as calcium retention capacity, albeit through an unknown mechanism.

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Mitochondrial control of apoptosis: an overview

Biochemical Society Symposium ◽

10.1042/bss0660001 ◽

1999 ◽

Vol 66 ◽

pp. 1-15 ◽

Cited By ~ 126

Author(s):

Guido Kroemer

Keyword(s):

Transmembrane Potential ◽

Mitochondrial Permeability Transition ◽

Ion Selectivity ◽

Permeability Transition ◽

Critical Event ◽

Intact Cells ◽

Isolated Mitochondria ◽

Pore Opening ◽

Mitochondrial Megachannel

The mitochondrial permeability transition (PT) pore, also called the mitochondrial megachannel, is a multiprotein complex formed at the contact site between the mitochondrial inner and outer membranes, exactly the same location at which Bax, Bcl-2 and Bcl-XL are particularly abundant. The PT pore participates in the regulation of matrix Ca2+, pH, transmembrane potential and volume, and functions as a Ca2+-, voltage-, pH- and redox-gated channel with several levels of conductance and little, if any, ion selectivity. We have obtained three independent lines of evidence implicating the mitochondrial PT pore in apoptosis. First, in intact cells, apoptosis is accompanied by an early dissipation of the mitochondrial transmembrane potential, ΔΨm. In several models of apoptosis, specific agents inhibiting the mitochondrial PT pore abolish this dissipation of the ΔΨm and simultaneously prevent activation of downstream caspases and endonucleases, indicating that PT pore opening can be a critical event of the apoptotic process. Secondly, mitochondria are rate-limiting for caspase and nuclease activation in several cell-free systems of apoptosis. Isolated mitochondria release apoptogenic factors capable of activating pro-caspases or endonucleases upon opening of the mitochondrial megachannel in vitro. Thirdly, opening of the purified PT pore complex reconstituted into liposomes is inhibited by recombinant Bcl-2 or Bcl-XL, two apoptosis-inhibitory proteins that also prevent PT pore opening in cells and isolated mitochondria. Altogether, our results suggest that PT pore opening is sufficient and (mostly) necessary for triggering apoptosis. The implications of these findings are examined in the light of pharmacological interventions in apoptosis.

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