DOCSLIB.ORG

Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): a Complex Relationship Regulated by the Camp/PKA Signaling Pathway

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): a Complex Relationship Regulated by the Camp/PKA Signaling Pathway cells Review Mitochondrial Biogenesis and Mitochondrial Reactive Oxygen Species (ROS): A Complex Relationship Regulated by the cAMP/PKA Signaling Pathway Cyrielle Bouchez 1,2 and Anne Devin 1,2,* 1 Université Bordeaux, IBGC, UMR 5095, 33077 Bordeaux CEDEX, France; [email protected] 2 Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, 1, rue Camille Saint Saëns, 33077 Bordeaux CEDEX, France * Correspondence: [email protected]; Tel.: +33-556-999-035; Fax: +33-556-999-040 Received: 28 February 2019; Accepted: 20 March 2019; Published: 27 March 2019 Abstract: Mitochondrial biogenesis is a complex process. It requires the contribution of both the nuclear and the mitochondrial genomes and therefore cross talk between the nucleus and mitochondria. Cellular energy demand can vary by great length and it is now well known that one way to adjust adenosine triphosphate (ATP) synthesis to energy demand is through modulation of mitochondrial content in eukaryotes. The knowledge of actors and signals regulating mitochondrial biogenesis is thus of high importance. Here, we review the regulation of mitochondrial biogenesis both in yeast and in mammalian cells through mitochondrial reactive oxygen species. Keywords: mitochondrial biogenesis; ROS; cAMP signaling; yeast 1. Introduction 1.1. Mitochondrial Oxidative Phosphorylation In eukaryotic cells, energy conversion processes are mandatory for both cell biomass generation and cellular maintenance. Adenosine triphosphate (ATP) is the cellular energy currency, and mitochondria play a crucial role in ATP synthesis thanks to the oxidative phosphorylation system (OXPHOS) located in the mitochondrial inner membrane. The oxidative part of this energy conversion process takes place in the four enzymatic complexes of the mitochondrial respiratory chain and leads to substrates—nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2)—oxidation. Activity of the respiratory chain is based on the transfer of two electrons from above-mentioned substrates to their final acceptor, the dioxygen. These redox reactions are coupled to proton extrusion at the level of complexes I, III, and IV in mammalian cells (Figure1A); thus, thanks to the inner mitochondrial membrane being quite impermeable, a proton gradient is generated across this membrane. The yeast Saccharomyces cerevisiae mitochondria do not harbor a proton-pumping complex I but rather a number of dehydrogenases (Figure1B) in the inner mitochondrial membrane [ 1]. The phosphorylating part of this process involves the ATPsynthase, the adenine nucleotide translocator (ANT), and the phosphate carrier. The proton gradient generated by the mitochondrial respiratory chain activity is used by the ATPsynthase for ATP synthesis from ADP and Pi and by a number of mitochondrial carriers. Cells 2019, 8, 287; doi:10.3390/cells8040287 www.mdpi.com/journal/cells Cells 2019, 8, 287 2 of 15 Cells 2019, 8, x FOR PEER REVIEW 2 of 15 FigureFigure 1. The 1. The oxidative oxidative phosphorylation phosphorylation system system (OXPHOS (OXPHOS)) system system in mammalian in mammalian cells (A cells) and( Ain) and in yeastyeast ((B) (modified (modified from from Rigoulet Rigoulet et al. 2010 et al. [2]). 2010Numbers [2]). represent Numbers respiratory represent chain respiratory complexes. I: chain complexes.proton-pumping I: proton-pumping nicotinamide nicotinamideadenine dinucleotide adenine ( dinucleotideNADH) dehydrogenase, (NADH) dehydrogenase,II: Succinate II: Succinatedehydrogenase; dehydrogenase; III: Cytochrome III: Cytochrome c reductase; c reductase; IV: Cytochrome IV: Cytochrome c oxidase. c oxidase. Adenine Adenine nucleotide nucleotide translocator (ANT) and Phosphate inorganic carrier are mitochondrial carriers. Gut2p is the glycerol- translocator (ANT) and Phosphate inorganic carrier are mitochondrial carriers. Gut2p is the 3-phosphate dehydrogenase in yeast. Dld1p is the lactate dehydrogenase in yeast. glycerol-3-phosphate dehydrogenase in yeast. Dld1p is the lactate dehydrogenase in yeast. 1.2. Mitochondrial1.2. Mitochondrial ROS ROS Production Production The main superoxide (O2.−) producer in the cell is the mitochondrial respiratory chain. This The main superoxide (O2· ) producer in the cell is the mitochondrial respiratory chain. production leads to hydrogen peroxide (H2O2) and hydroxyl radical (.HO) formation. Superoxide · This productionformation occurs leads when to hydrogen a unique peroxideelectron is(H accepted2O2) and by hydroxylthe ground radical state oxygen. ( HO) Consequently, formation. Superoxide any formationelectron occurs transfer when that ainvolves unique a electronunique electron is accepted is susceptible by the ground of superoxide state oxygen.generation. Consequently, This is any electronparticularly transfer true in that membranes, involves w ahere unique oxygen electron solubility is susceptible is high. The of respiratory superoxide chain generation. complexes ThisI is particularlyand III have true long in membranes, been studied for where their oxygen contribution solubility to mitochondrial is high. The reactive respiratory oxygen chainspecies complexes (ROS) I and IIIproduction have long [3– been8]. In studiedcomplex forIII, superoxide their contribution formation to is mitochondrial due to the Q cycle reactive [9], and oxygen ROS production species (ROS) productioncan take [3 –place8]. In both complex in the III, mitochondrial superoxide formation matrix and is duein the to theintermembrane Q cycle [9], and space. ROS Besides production the can takecontribution place both in of the these mitochondrial complexes to matrixmitochondrial and in theROS intermembrane production, mitochondrial space. Besides dehydrogenases the contribution are involved in ROS formation as well. For example, α-ketoglutarate dehydrogenase catalyses the of these complexes to mitochondrial ROS production, mitochondrial dehydrogenases are involved oxidation of α-ketoglutarate in succinyl-coA with the generation of NADH. Single electron transfer in ROS formation as well. For example, α-ketoglutarate dehydrogenase catalyses the oxidation of occurs within this enzyme, and its activity can thus be associated with ROS production in the Krebs α-ketoglutarate in succinyl-coA with the generation of NADH. Single electron transfer occurs within this enzyme, and its activity can thus be associated with ROS production in the Krebs cycle [10]. For the same reason, the mitochondrial glycerol-3-phosphate dehydrogenase (G3PDH) produces ROS [11,12]. CellsCells 20192019, ,88, ,x 287 FOR PEER REVIEW 33 of of 15 15 cycle [10]. For the same reason, the mitochondrial glycerol-3-phosphate dehydrogenase (G3PDH) producesAs stated above,ROS [11,12] the yeast. AsSaccharomyces stated above, cerevisiae the yeastharbors Saccharomyces two NADH-dehydrogenases, cerevisiae harbors whichtwo NADH are sites- dehydrogenases,of ROS production which as well. are sites of ROS production as well. InIn this this review, review, we we will will address address the the relationships relationships between between mitochondrial mitochondrial ROS ROS production production and and thethe regulation regulation of of mitochondrial mitochondrial biogenesis biogenesis (i.e. (i.e.,, the the biogenesis biogenesis of of the the whole whole compartment compartment and and more more particularlyparticularly of of the the OXPHOS OXPHOS system) system) both both in in yeast yeast and and in in mammalian mammalian cells. cells. 2.2. Mitochondrial Mitochondrial Compart Compartmentment Biogenesis Biogenesis MitochondrialMitochondrial biogenesis biogenesis is is a a complex complex process. process. Indeed, Indeed, mitochondria mitochondria are are organelles organelles that that harbor harbor theirtheir own own genome genome (mtDNA) (mtDNA).. In In mammalian mammalian cells, cells, mtDNA mtDNA is a is circular a circular molecule, molecule, which which encodes encodes for 13for mRNAs, 13 mRNAs, 22 tRNAs, 22 tRNAs, and and 2 rRNAs. 2 rRNAs. All All13 13mRNAs mRNAs of ofmt mtDNADNA encode encode 11 11 subunits subunits of of the the ETC ETC complexescomplexes II (7),(7), III III (1) (1) and and IV (3),IV and(3), 2 and subunits 2 subunits of ATP synthaseof ATP (complexsynthase V).(complex However, V) mitochondria. However, mitochondriaare genetically are semiautonomous genetically semiautonomous and strongly rely and on strongly the nuclear rely genome on the fornuclear their biologicalgenome for function. their biologicalThus, mitochondrial function. Thus, biogenesis mitochondri necessitatesal biogenesis the coordinated necessitates expression the coordinated of both expression mitochondrial of both and mitochondrialnuclear genomes. and nuclear genomes. InIn the the yeast yeast SaccharomycesSaccharomyces cerevisiae cerevisiae ((FigureFigure 22),), mitochondrialmitochondrial biogenesisbiogenesis is regulatedregulated atat thethe transcriptionaltranscriptional level, level, by by nuclear nuclear proteins. proteins. The The main main actor actor of of th thisis process process is is a a transcription transcription complex complex composedcomposed of of four four proteins proteins that that belong belong to tothe the same same family: family: heme heme activator activator proteins proteins (Hap) (Hap) 2, 3, 4 2,, and 3, 4, 5and [13– 517] [13. Hap2p,–17]. Hap2p, Hap3p, Hap3p, and Hap5p and form Hap5p a complex form a complexthat is bound that isto boundnuclear to DNA, nuclear and DNA, Hap4p and is theHap4p co-activator is the co-activator of this complex, of this
Load more

Recommended publications
  • Alternative Oxidase: a Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis During Abiotic and Biotic Stress in Plants
    Int. J. Mol. Sci. 2013, 14, 6805-6847; doi:10.3390/ijms14046805 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants Greg C. Vanlerberghe Department of Biological Sciences and Department of Cell and Systems Biology, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C1A4, Canada; E-Mail: [email protected]; Tel.: +1-416-208-2742; Fax: +1-416-287-7676 Received: 16 February 2013; in revised form: 8 March 2013 / Accepted: 12 March 2013 / Published: 26 March 2013 Abstract: Alternative oxidase (AOX) is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain. While respiratory carbon oxidation pathways, electron transport, and ATP turnover are tightly coupled processes, AOX provides a means to relax this coupling, thus providing a degree of metabolic homeostasis to carbon and energy metabolism. Beside their role in primary metabolism, plant mitochondria also act as “signaling organelles”, able to influence processes such as nuclear gene expression. AOX activity can control the level of potential mitochondrial signaling molecules such as superoxide, nitric oxide and important redox couples. In this way, AOX also provides a degree of signaling homeostasis to the organelle. Evidence suggests that AOX function in metabolic and signaling homeostasis is particularly important during stress. These include abiotic stresses such as low temperature, drought, and nutrient deficiency, as well as biotic stresses such as bacterial infection. This review provides an introduction to the genetic and biochemical control of AOX respiration, as well as providing generalized examples of how AOX activity can provide metabolic and signaling homeostasis.
    [Show full text]
  • IDH2 Deficiency Impairs Cutaneous Wound Healing Via ROS-Dependent
    BBA - Molecular Basis of Disease 1865 (2019) 165523 Contents lists available at ScienceDirect BBA - Molecular Basis of Disease journal homepage: www.elsevier.com/locate/bbadis IDH2 deficiency impairs cutaneous wound healing via ROS-dependent apoptosis T ⁎ Sung Hwan Kim, Jeen-Woo Park School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Taegu, Republic of Korea ARTICLE INFO ABSTRACT Keywords: Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue that play a Wound healing pivotal role in cutaneous wound healing by synthesizing fibronectin (a component of the extracellular matrix), Apoptosis secreting angiogenesis factors, and generating strong contractile forces. In wound healing, low concentrations of IDH2 reactive oxygen species (ROS) are essential in combating invading microorganisms and in cell-survival signaling. Mitochondria However, excessive ROS production impairs fibroblasts. Mitochondrial NADP+-dependent isocitrate dehy- Mito-TEMPO drogenase (IDH2) is a key enzyme that regulates the mitochondrial redox balance and reduces oxidative stress- induced cell injury through the generation of NADPH. In the present study, the downregulation of IDH2 ex- pression resulted in an increase in cell apoptosis in mouse skin through ROS-dependent ATM-mediated p53 signaling. IDH2 deficiency also delayed cutaneous wound healing in mice and impaired dermal fibroblast function. Furthermore, pretreatment with the mitochondria-targeted antioxidant mito-TEMPO alleviated the apoptosis induced by IDH2 deficiency both in vitro and in vivo. Together, our findings highlight the role of IDH2 in cutaneous wound healing in association with mitochondrial ROS. 1. Introduction expression, while also stimulating the proliferation and migration of fibroblasts, leading to the formation of the extracellular matrix (ECM).
    [Show full text]
  • Melatonin Induces Apoptosis in Cholangiocarcinoma Cell Lines by Activating the Reactive Oxygen Species-Mediated Mitochondrial Pathway
    ONCOLOGY REPORTS 33: 1443-1449, 2015 Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway Umawadee LAOTHONG1-3,5, YUSUKE HIRAKU2, SHINJI Oikawa2, KITTI INTUYOD3,4, MARIKO Murata2* and SOMCHAI PINLAOR1,3* 1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 2Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507, Japan; 3Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 4Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand Received November 26, 2014; Accepted January 2, 2015 DOI: 10.3892/or.2015.3738 Abstract. We previously demonstrated that melatonin could pro-oxidant by activating ROS-dependent DNA damage and be used as a chemopreventive agent for inhibiting cholangio- thus leading to the apoptosis of CCA cells. carcinoma (CCA) development in a hamster model. However, the cytotoxic activity of melatonin in cancer remains unclear. Introduction In the present study, we investigated the effect of melatonin on CCA cell lines. Human CCA cell lines (KKU-M055 and Cholangiocarcinoma (CCA) is a devastating biliary cancer that KKU-M214) were treated with melatonin at concentrations poses continuing diagnostic and therapeutic challenges (1). of 0.5, 1 and 2 mM for 48 h. Melatonin treatment exerted a There are several risk factors for CCA: mainly liver fluke cytotoxic effect on CCA cells by inhibiting CCA cell viability infection, primary sclerosing cholangitis, biliary-duct cysts in a concentration-dependent manner. Treatment with mela- and hepatolithiasis (2). The highest prevalence of liver fluke tonin, especially at 2 mM, increased intracellular reactive Opisthorchis viverrini infection has been reported in Northeast oxygen species (ROS) production and in turn led to increased Thailand, where CCA incidence is also high (3).
    [Show full text]
  • Mitochondria's Role in Skin Ageing
    biology Review Mitochondria’s Role in Skin Ageing Roisin Stout and Mark Birch-Machin * Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; [email protected] * Correspondence: [email protected] Received: 21 December 2018; Accepted: 7 February 2019; Published: 11 May 2019 Abstract: Skin ageing is the result of a loss of cellular function, which can be further accelerated by external factors. Mitochondria have important roles in skin function, and mitochondrial damage has been found to accumulate with age in skin cells, but also in response to solar light and pollution. There is increasing evidence that mitochondrial dysfunction and oxidative stress are key features in all ageing tissues, including skin. This is directly linked to skin ageing phenotypes: wrinkle formation, hair greying and loss, uneven pigmentation and decreased wound healing. The loss of barrier function during skin ageing increases susceptibility to infection and affects wound healing. Therefore, an understanding of the mechanisms involved is important clinically and also for the development of antiageing skin care products. Keywords: mitochondria; skin; ageing; reactive oxygen species; photoageing 1. Skin Structure Skin is the largest organ of the human body and made up of three distinct layers: the epidermis, the dermis and subcutaneous fat. It functions as a barrier against the environment, providing protection against microbes as well as fluid and temperature homeostasis. The epidermis is a thin layer of densely packed keratinised epithelial cells (keratinocytes) which contains no nerves or blood vessels and relies on the thick dermal layer underneath for metabolism.
    [Show full text]
  • Base Excision Repair Synthesis of DNA Containing 8-Oxoguanine in Escherichia Coli
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 35, No. 2, 106-112, April 2003 Base excision repair synthesis of DNA containing 8-oxoguanine in Escherichia coli Yun-Song Lee1,3 and Myung-Hee Chung2 Introduction 1Division of Pharmacology 8-oxo-7,8-dihydroguanine (8-oxo-G) in DNA is a muta- Department of Molecular and Cellular Biology genic adduct formed by reactive oxygen species Sungkyunkwan University School of Medicine (Kasai and Nishimura, 1984). As a structural prefe- Suwon 440-746, Korea rence, adenine is frequently incorporated into oppo- 2Department of Pharmacology site template 8-oxo-G (Shibutani et al., 1991), and 8- Seoul National University College of Medicine oxo-dGTP is incorporated into opposite template dA Jongno-gu, Seoul 110-799, Korea during DNA synthesis (Cheng et al., 1992). Thus, un- 3Corresponding author: Tel, 82-31-299-6190; repaired, these mismatches lead to GT and AC trans- Fax, 82-31-299-6209; E-mail, [email protected] versions, respectively (Grollman and Morya, 1993). In Escherichia coli, several DNA repair enzymes, Accepted 29 March 2003 preventing mutagenesis by 8-oxo-G, are known as the GO system (Michaels et al., 1992). The GO system Abbreviations: 8-oxo-G, 8-oxo-7,8-dihydroguanine; Fapy, 2,6-dihy- consists of MutT (8-oxo-dGTPase), MutM (2,6-dihydro- droxy-5N-formamidopyrimidine; FPG, Fapy-DNA glycosylase; BER, xy-5N-formamidopyrimidine (Fapy)-DNA glycosylase, base excision repair; AP, apurinic/apyrimidinic; dRPase, deoxyribo- Fpg) and MutY (adenine-DNA glycosylase). 8-oxo- phosphatase GTPase prevents incorporation of 8-oxo-dGTP into DNA by degrading 8-oxo-dGTP.
    [Show full text]
  • Roles of Mitochondrial Respiratory Complexes During Infection Pedro Escoll, Lucien Platon, Carmen Buchrieser
    Roles of Mitochondrial Respiratory Complexes during Infection Pedro Escoll, Lucien Platon, Carmen Buchrieser To cite this version: Pedro Escoll, Lucien Platon, Carmen Buchrieser. Roles of Mitochondrial Respiratory Complexes during Infection. Immunometabolism, Hapres, 2019, Immunometabolism and Inflammation, 1, pp.e190011. 10.20900/immunometab20190011. pasteur-02593579 HAL Id: pasteur-02593579 https://hal-pasteur.archives-ouvertes.fr/pasteur-02593579 Submitted on 15 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License ij.hapres.com Review Roles of Mitochondrial Respiratory Complexes during Infection Pedro Escoll 1,2,*, Lucien Platon 1,2,3, Carmen Buchrieser 1,2,* 1 Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, 75015 Paris, France 2 CNRS-UMR 3525, 75015 Paris, France 3 Faculté des Sciences, Université de Montpellier, 34095 Montpellier, France * Correspondence: Pedro Escoll, Email: [email protected]; Tel.: +33-0-1-44-38-9540; Carmen Buchrieser, Email: [email protected]; Tel.: +33-0-1-45-68-8372. ABSTRACT Beyond oxidative phosphorylation (OXPHOS), mitochondria have also immune functions against infection, such as the regulation of cytokine production, the generation of metabolites with antimicrobial proprieties and the regulation of inflammasome-dependent cell death, which seem in turn to be regulated by the metabolic status of the organelle.
    [Show full text]
  • Reactive Oxygen Species from Chloroplasts Contribute to 3-Acetyl-5- Isopropyltetramic Acid-Induced Leaf Necrosis of Arabidopsis Thaliana
    Plant Physiology and Biochemistry 52 (2012) 38e51 Contents lists available at SciVerse ScienceDirect Plant Physiology and Biochemistry journal homepage: www.elsevier.com/locate/plaphy Research article Reactive oxygen species from chloroplasts contribute to 3-acetyl-5- isopropyltetramic acid-induced leaf necrosis of Arabidopsis thaliana Shiguo Chen a,1, Chunyan Yin a,1, Reto Jörg Strasser a,b,c, Govindjee d,2, Chunlong Yang a, Sheng Qiang a,* a Weed Research Laboratory, Nanjing Agricultural University, Nanjing 210095, China b Bioenergetics Laboratory, University of Geneva, CH-1254 Jussy/Geneva, Switzerland c North West University of South Africa, South Africa d Department of Plant Biology, and Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA article info abstract Article history: 3-Acetyl-5-isopropyltetramic acid (3-AIPTA), a derivate of tetramic acid, is responsible for brown leaf- Received 22 August 2011 spot disease in many plants and often kills seedlings of both mono- and dicotyledonous plants. To further Accepted 2 November 2011 elucidate the mode of action of 3-AIPTA, during 3-AIPTA-induced cell necrosis, a series of experiments Available online 11 November 2011 were performed to assess the role of reactive oxygen species (ROS) in this process. When Arabidopsis thaliana leaves were incubated with 3-AIPTA, photosystem II (PSII) electron transport beyond QA (the Keywords: primary plastoquinone acceptor of PSII) and the reduction of the end acceptors at the PSI acceptor side 3-AIPTA (3-acetyl-5-isopropyltetramic acid) were inhibited; this was followed by increase in charge recombination and electron leakage to O , ROS (reactive oxygen species) 2 Cell death resulting in chloroplast-derived oxidative burst.
    [Show full text]
  • Oxidative Phosphorylation Efficiency, Proton
    © 2015. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2015) 218, 3222-3228 doi:10.1242/jeb.126086 RESEARCH ARTICLE Oxidative phosphorylation efficiency, proton conductance and reactive oxygen species production of liver mitochondria correlates with body mass in frogs Damien Roussel1,*, Karine Salin1,2, Adeline Dumet1, Caroline Romestaing1, Benjamin Rey3,4 and Yann Voituron1 ABSTRACT (Schmidt-Nielsen, 1984; Darveau et al., 2002; Glazier, 2005). Most Body size is a central biological parameter affecting most biological notably, basal metabolic rate in mammals and birds has been processes (especially energetics) and the mitochondrion is a key correlated with many energy-consuming processes at the level of organelle controlling metabolism and is also the cell’s main source of tissues, cells and mitochondria (Kunkel and Campbell, 1952; chemical energy. However, the link between body size and Hulbert and Else, 2000; Else et al., 2004), providing support for the ‘ ’ mitochondrial function is still unclear, especially in ectotherms. In this multiple-causes model of allometry (Darveau et al., 2002). M study, we investigated several parameters of mitochondrial Research has focused on the relationship between body mass ( b) bioenergetics in the liver of three closely related species of frog (the and mitochondrial function (Darveau et al., 2002; Brand et al., 2003; common frog Rana temporaria, the marsh frog Pelophylax ridibundus Porter and Brand, 1993). Understanding the link between body size and the bull frog Lithobates catesbeiana). These particular species and mitochondrial bioenergetics is of fundamental importance as were chosen because of their differences in adult body mass. We found mitochondria are essential organelles of eukaryotic cells responsible that mitochondrial coupling efficiency was markedly increased with for the biosynthesis of many cellular metabolites and the generation animal size, which led to a higher ATP production (+70%) in the larger of chemical energy in the form of ATP (Brand, 2005).
    [Show full text]
  • Mitochondrial ATP Is Required for the Maintenance of Membrane Integrity
    REPRODUCTIONRESEARCH Mitochondrial ATP is required for the maintenance of membrane integrity in stallion spermatozoa, whereas motility requires both glycolysis and oxidative phosphorylation M Plaza Davila1, P Martin Muñoz1, J M Gallardo Bolaños1, T A E Stout2,3, B M Gadella3,4, J A Tapia5, C Balao da Silva6, C Ortega Ferrusola7 and F J Peña1 1Laboratory of Equine Reproduction and Equine Spermatology. Veterinary Teaching Hospital, University of Extremadura, Cáceres, Spain, 2Department of Equine Sciences, 3Department of Farm Animal Health, 4Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, 5Department of Physiology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain, 6Portalagre Polytechnic Institute, Superior Agriculture School of Elvas, Elvas, Portugal and 7Reproduction and Obstetrics Department of Animal Medicine and Surgery, University of León, León, Spain Correspondence should be addressed to F J Peña; Email: [email protected] Abstract To investigate the hypothesis that oxidative phosphorylation is a major source of ATP to fuel stallion sperm motility, oxidative phosphorylation was suppressed using the mitochondrial uncouplers CCCP and 2,4,-dinitrophenol (DNP) and by inhibiting mitochondrial respiration at complex IV using sodium cyanide or at the level of ATP synthase using oligomycin-A. As mitochondrial dysfunction may also lead to oxidative stress, production of reactive oxygen species was monitored simultaneously. All inhibitors reduced ATP content, but oligomycin-A did so most profoundly. Oligomycin-A and CCCP also significantly reduced mitochondrial membrane potential. Sperm motility almost completely ceased after the inhibition of mitochondrial respiration and both percentage of motile sperm and sperm velocity were reduced in the presence of mitochondrial uncouplers.
    [Show full text]
  • Mitochondria As Regulators of Reactive Oxygen Species Daniel Munro1,2 and Jason R
    © 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2017) 220, 1170-1180 doi:10.1242/jeb.132142 COMMENTARY A radical shift in perspective: mitochondria as regulators of reactive oxygen species Daniel Munro1,2 and Jason R. Treberg1,2,3,* ABSTRACT prolonged activity, and even senescence and ageing (Trushina and Mitochondria are widely recognized as a source of reactive oxygen McMurray, 2007; Costantini, 2008; Monaghan et al., 2009; Dai species (ROS) in animal cells, where it is assumed that over- et al., 2014; Day, 2014; Mason and Wadley, 2014). For example, production of ROS leads to an overwhelmed antioxidant system and during migration, a trade-off may occur between individual oxidative stress. In this Commentary, we describe a more nuanced performance and survival or reproductive fitness, owing to model of mitochondrial ROS metabolism, where integration of ROS oxidative damage accrued during intense exercise. Publications in production with consumption by the mitochondrial antioxidant these areas, and many others, often describe mitochondria as the ‘ ’ pathways may lead to the regulation of ROS levels. Superoxide and major source of ROS in animal cells, despite the high antioxidant capacity of mitochondria (Zoccorato et al., 2004; Dreschel and hydrogen peroxide (H2O2) are the main ROS formed by mitochondria. However, superoxide, a free radical, is converted to the non-radical, Patel, 2010; Banh and Treberg, 2013). However, the rationale behind the notion of mitochondria as the major source of ROS in membrane-permeant H2O2; consequently, ROS may readily cross cellular compartments. By combining measurements of production animal cells has been questioned (Brown and Borutaite, 2012), if not directly challenged, based on the capacity of isolated and consumption of H2O2, it can be shown that isolated mitochondria mitochondria to consume substantial amounts of ROS (Zoccorato can intrinsically approach a steady-state concentration of H2O2 in the medium.
    [Show full text]
  • Oxidative Stress, Mitochondrial Dysfunction, and Aging
    University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2012-10 Oxidative stress, mitochondrial dysfunction, and aging Hang Cui University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Cell Biology Commons, and the Physiology Commons Repository Citation Cui H, Kong Y, Zhang H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. Open Access Articles. https://doi.org/10.1155/2012/646354. Retrieved from https://escholarship.umassmed.edu/ oapubs/2303 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Hindawi Publishing Corporation Journal of Signal Transduction Volume 2012, Article ID 646354, 13 pages doi:10.1155/2012/646354 Review Article Oxidative Stress, Mitochondrial Dysfunction, and Aging Hang Cui, Yahui Kong, and Hong Zhang Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA Correspondence should be addressed to Hong Zhang, [email protected] Received 15 May 2011; Accepted 3 August 2011 Academic Editor: Paolo Pinton Copyright © 2012 Hang Cui et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases.
    [Show full text]
  • ATM-Mediated Mitochondrial Radiation Responses of Human Fibroblasts
    G C A T T A C G G C A T genes Review ATM-Mediated Mitochondrial Radiation Responses of Human Fibroblasts Tsutomu Shimura Department of Environmental Health, National Institute of Public Health 2-3-6 Minami, Wako 351-0197, Saitama, Japan; [email protected]; Tel.: +81-48-458-6261 Abstract: Ataxia telangiectasia (AT) is characterized by extreme sensitivity to ionizing radiation. The gene mutated in AT, Ataxia Telangiectasia Mutated (ATM), has serine/threonine protein kinase activ- ity and mediates the activation of multiple signal transduction pathways involved in the processing of DNA double-strand breaks. Reactive oxygen species (ROS) created as a byproduct of the mito- chondria’s oxidative phosphorylation (OXPHOS) has been proposed to be the source of intracellular ROS. Mitochondria are uniquely vulnerable to ROS because they are the sites of ROS generation. ROS- induced mitochondrial mutations lead to impaired mitochondrial respiration and further increase the likelihood of ROS generation, establishing a vicious cycle of further ROS production and mitochon- drial damage. AT patients and ATM-deficient mice display intrinsic mitochondrial dysfunction and exhibit constitutive elevations in ROS levels. ATM plays a critical role in maintaining cellular redox homeostasis. However, the precise mechanism of ATM-mediated mitochondrial antioxidants remains unclear. The aim of this review paper is to introduce our current research surrounding the role of ATM on maintaining cellular redox control in human fibroblasts. ATM-mediated signal transduction is important in the mitochondrial radiation response. Perturbation of mitochondrial redox control elevates ROS which are key mediators in the development of cancer by many mechanisms, including ROS-mediated genomic instability, tumor microenvironment formation, and chronic inflammation.
    [Show full text]