scholarly journals Transmission of Functional, Wild-Type Mitochondria and the Fittest mtDNA to the Next Generation: Bottleneck Phenomenon, Balbiani Body, and Mitophagy

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 104 ◽  
Author(s):  
Waclaw Tworzydlo ◽  
Malgorzata Sekula ◽  
Szczepan M. Bilinski
Keyword(s):  
Membrane Potential ◽  
Respiratory Activity ◽  
Metabolic Energy ◽  
Oxygen Species ◽  
Deleterious Mutations ◽  
Next Generation ◽  
Wild Type ◽  
Female Germline ◽  
Final Effect

The most important role of mitochondria is to supply cells with metabolic energy in the form of adenosine triphosphate (ATP). As synthesis of ATP molecules is accompanied by the generation of reactive oxygen species (ROS), mitochondrial DNA (mtDNA) is highly vulnerable to impairment and, consequently, accumulation of deleterious mutations. In most animals, mitochondria are transmitted to the next generation maternally, i.e., exclusively from female germline cells (oocytes and eggs). It has been suggested, in this context, that a specialized mechanism must operate in the developing oocytes enabling escape from the impairment and subsequent transmission of accurate (devoid of mutations) mtDNA from one generation to the next. Literature survey suggest that two distinct and irreplaceable pathways of mitochondria transmission may be operational in various animal lineages. In some taxa, the mitochondria are apparently selected: functional mitochondria with high inner membrane potential are transferred to the cells of the embryo, whereas those with low membrane potential (overloaded with mutations in mtDNA) are eliminated by mitophagy. In other species, the respiratory activity of germline mitochondria is suppressed and ROS production alleviated leading to the same final effect, i.e., transmission of undamaged mitochondria to offspring, via an entirely different route.

scholarly journals Role of Homologous Recombination Genes in Repair of Alkylation Base Damage by Candida albicans

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 447 ◽  
Author(s):  
Toni Ciudad ◽  
Alberto Bellido ◽  
Encarnación Andaluz ◽  
Belén Hermosa ◽  
Germán Larriba
Keyword(s):  
Candida Albicans ◽  
Homologous Recombination ◽  
Excision Repair ◽  
Metabolic Energy ◽  
Resting Cells ◽  
Wild Type ◽  
Base Damage

Candida albicans mutants deficient in homologous recombination (HR) are extremely sensitive to the alkylating agent methyl-methane-sulfonate (MMS). Here, we have investigated the role of HR genes in the protection and repair of C. albicans chromosomes by taking advantage of the heat-labile property (55 °C) of MMS-induced base damage. Acute MMS treatments of cycling cells caused chromosome fragmentation in vitro (55 °C) due to the generation of heat-dependent breaks (HDBs), but not in vivo (30 °C). Following removal of MMS wild type, cells regained the chromosome ladder regardless of whether they were transferred to yeast extract/peptone/dextrose (YPD) or to phosphate buffer saline (PBS); however, repair of HDB/chromosome restitution was faster in YPD, suggesting that it was accelerated by metabolic energy and further fueled by the subsequent overgrowth of survivors. Compared to wild type CAI4, chromosome restitution in YPD was not altered in a Carad59 isogenic derivative, whereas it was significantly delayed in Carad51 and Carad52 counterparts. However, when post-MMS incubation took place in PBS, chromosome restitution in wild type and HR mutants occurred with similar kinetics, suggesting that the exquisite sensitivity of Carad51 and Carad52 mutants to MMS is due to defective fork restart. Overall, our results demonstrate that repair of HDBs by resting cells of C. albicans is rather independent of CaRad51, CaRad52, and CaRad59, suggesting that it occurs mainly by base excision repair (BER).

Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse

2005 ◽  
Vol 289 (1) ◽  
pp. H181-H187 ◽  
Author(s):  
Jong Woong Park ◽  
Wen-Ning Qi ◽  
Yongting Cai ◽  
Igor Zelko ◽  
John Q. Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Histological Analysis ◽  
Extracellular Superoxide Dismutase ◽  
Mrna Levels ◽  
Oxygen Species ◽  
Wild Type ◽  
Muscle Flaps ◽  
Protein Levels ◽  
Muscle Ischemia

This study investigates the role of extracellular SOD (EC-SOD), the major extracellular antioxidant enzyme, in skeletal muscle ischemia and reperfusion (I/R) injury. Pedicled cremaster muscle flaps from homozygous EC-SOD knockout (EC-SOD−/−) and wild-type (WT) mice were subjected to 4.5-h ischemia and 90-min reperfusion followed by functional and molecular analyses. Our results revealed that EC-SOD−/− mice showed significantly profound I/R injury compared with WT littermates. In particular, there was a delayed and incomplete recovery of arterial spasm and blood flow during reperfusion, and more severe acute inflammatory reaction and muscle damage were noted in EC-SOD−/− mice. After 90-min reperfusion, intracellular SOD [copper- and zinc-containing SOD (CuZn-SOD) and manganese-containing (Mn-SOD)] mRNA levels decreased similarly in both groups. EC-SOD mRNA levels increased in WT mice, whereas EC-SOD mRNA was undetectable, as expected, in EC-SOD−/− mice. In both groups of animals, CuZn-SOD protein levels decreased and Mn-SOD protein levels remained unchanged. EC-SOD protein levels decreased in WT mice. Histological analysis showed diffuse edema and inflammation around muscle fibers, which was more pronounced in EC-SOD−/− mice. In conclusion, our data suggest that EC-SOD plays an important role in the protection from skeletal muscle I/R injury caused by excessive generation of reactive oxygen species.

scholarly journals Pyrophosphate Stimulates the Phosphate-Sodium Symporter ofTrypanosoma bruceiAcidocalcisomes andSaccharomyces cerevisiaeVacuoles

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Evgeniy Potapenko ◽  
Ciro D. Cordeiro ◽  
Guozhong Huang ◽  
Roberto Docampo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Membrane Potential ◽  
Trypanosoma Brucei ◽  
Wild Type ◽  
Inorganic Pyrophosphate ◽  
Content Type ◽  
Yeast Strains ◽  
Outward Currents ◽  
Sodium Dependent

ABSTRACTInorganic pyrophosphate (PPi) is a by-product of biosynthetic reactions and has bioenergetic and regulatory roles in a variety of cells. Here we show that PPiand other pyrophosphate-containing compounds, including polyphosphate (polyP), can stimulate sodium-dependent depolarization of the membrane potential and Piconductance inXenopusoocytes expressing aSaccharomyces cerevisiaeorTrypanosoma bruceiNa+/Pisymporter. PPiis not taken up byXenopusoocytes, and deletion of the TbPho91 SPX domain abolished its depolarizing effect. PPigenerated outward currents in Na+/Pi-loaded giant vacuoles prepared from wild-type orpho91Δ yeast strains expressingTbPHO91but not from thepho91Δstrains. Our results suggest that PPi, at physiological concentrations, can function as a signaling molecule releasing PifromS. cerevisiaevacuoles andT. bruceiacidocalcisomes.IMPORTANCEAcidocalcisomes, first described in trypanosomes and known to be present in a variety of cells, have similarities withS. cerevisiaevacuoles in their structure and composition. Both organelles share a Na+/Pisymporter involved in Pirelease to the cytosol, where it is needed for biosynthetic reactions. Here we show that PPi, at physiological cytosolic concentrations, stimulates the symporter expressed in eitherXenopusoocytes or yeast vacuoles via its SPX domain, revealing a signaling role of this molecule.

scholarly journals Protection of Mycobacterium tuberculosis from Reactive Oxygen Species Conferred by the mel2 Locus Impacts Persistence and Dissemination

2009 ◽  
Vol 77 (6) ◽  
pp. 2557-2567 ◽  
Author(s):  
Suat L. G. Cirillo ◽  
Selvakumar Subbian ◽  
Bing Chen ◽  
Torin R. Weisbrod ◽  
William R. Jacobs ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Bacterial Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Wild Type ◽  
Primary Mechanism ◽  
Insight Into ◽  
Increased Susceptibility

ABSTRACT Persistence of Mycobacterium tuberculosis in humans represents a major roadblock to elimination of tuberculosis. We describe identification of a locus in M. tuberculosis, mel2, that displays similarity to bacterial bioluminescent loci and plays an important role during persistence in mice. We constructed a deletion of the mel2 locus and found that the mutant displays increased susceptibility to reactive oxygen species (ROS). Upon infection of mice by aerosol the mutant grows normally until the persistent stage, where it does not persist as well as wild type. Histopathological analyses show that infection with the mel2 mutant results in reduced pathology and both CFU and histopathology indicate that dissemination of the mel2 mutant to the spleen is delayed. These data along with growth in activated macrophages and infection of Phox−/− and iNOS−/− mice and bone marrow-derived macrophages suggest that the primary mechanism by which mel2 affects pathogenesis is through its ability to confer resistance to ROS. These studies provide the first insight into the mechanism of action for this novel class of genes that are related to bioluminescence genes. The role of mel2 in resistance to ROS is important for persistence and dissemination of M. tuberculosis and suggests that homologues in other bacterial species are likely to play a role in pathogenesis.

scholarly journals Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice

2020 ◽  
Vol 21 (9) ◽  
pp. 3261 ◽  
Author(s):  
Sheng-Min Hsu ◽  
Chang-Hao Yang ◽  
Yu-Ti Teng ◽  
Hsien-Yang Tsai ◽  
Chieh-Yu Lin ◽  
...  
Keyword(s):  
Reactive Oxygen ◽  
Oxygen Species ◽  
Wild Type ◽  
Experimental Autoimmune Uveitis ◽  
Autoimmune Uveitis ◽  
Monocyte Chemoattractant ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Reactive oxygen species (ROS) are produced by host phagocytes and play an important role in antimicrobial actions against various pathogens. Autoimmune uveitis causes blindness and severe visual impairment in humans at all ages worldwide. However, the role of ROS in autoimmune uveitis remains unclear. We used ROS-deficient (Ncf1−/−) mice to investigate the role of ROS in experimental autoimmune uveitis (EAU). Besides, we also used the antioxidant N-acetylcysteine (NAC) treatment to evaluate the effect of suppression of ROS on EAU in mice. The EAU disease scores of Ncf1−/− mice were significantly lower than those of wild-type mice. EAU induction increased the levels of cytokines (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-12, IL-17, and tumor necrosis factor (TNF)-α) and chemokines (monocyte chemoattractant protein (MCP)-1) in the retinas of wild-type mice but not in those of Ncf1−/− mice. EAU induction enhanced the level of NF-κB activity in wild-type mice. However, the level of NF-κB activity in Ncf1−/− mice with EAU induction was low. Treatment with the antioxidant NAC also decreased the severity of EAU in mice with reduced levels of oxidative stress, inflammatory mediators, and NF-κB activation in the retina. We successfully revealed a novel role of ROS in the pathogenesis of EAU and suggest a potential antioxidant role for the treatment of autoimmune uveitis in the future.

Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans

2006 ◽  
Vol 55 (9) ◽  
pp. 1291-1299 ◽  
Author(s):  
Yasuaki Aratani ◽  
Fumiaki Kura ◽  
Haruo Watanabe ◽  
Hisayoshi Akagawa ◽  
Yukie Takano ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Pulmonary Infection ◽  
Severe Pneumonia ◽  
Oxygen Species ◽  
Wild Type ◽  
Hypohalous Acids ◽  
The Brain ◽  
Oxidative System

The in vivo contribution of reactive oxygen species produced by neutrophils against Cryptococcus infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from H2O2. This study investigated the role of MPO in immunological defence against Cryptococcus neoformans in an MPO-deficient (MPO−/−) mouse model. The survival of MPO−/− mice infected either intranasally or intravenously with C. neoformans was lower than that of identically challenged wild-type mice. The MPO−/− mice that received intranasal injection of C. neoformans had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO−/− mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)-γ than wild-type mice, suggesting a weak Th1 response in the MPO−/− mice to C. neoformans. Pathologically, the MPO−/− mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1α/β in the lungs. In addition, in MPO−/− mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-derived cytokine (KC) level in the brain of infected MPO−/− mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO−/− mice compared to wild-type, suggesting decreased resistance to C. neoformans not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.

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