Mitochondrial Genome (mtDNA) Mutations that Generate Reactive Oxygen Species

Hahn, Anne; Zuryn, Steven

doi:10.3390/antiox8090392

Cited by 109 publications

(78 citation statements)

References 108 publications

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“…Nitric oxide synthase is activated by Ca 2+ to produce nitric oxide (NO), leading to oxidative stress in mitochondria (23). Consistent with this, the levels of several mitochondrial genes encoding complex I, III, and IV protein showed a subtle, but significant, up-regulation (SI Appendix, Table S2) (39). NADPH oxidase, encoded by Nox and Duox, catalyze the production of a superoxide free radical by transferring one electron to oxygen from NADPH (40).…”

Section: Imidacloprid Perturbs the Expression Of Genes Related To Stressmentioning

confidence: 66%

Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila

Martelli

Zuo

Wang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

107

112

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Declining insect population sizes are provoking grave concern around the world as insects play essential roles in food production and ecosystems. Environmental contamination by intense insecticide usage is consistently proposed as a significant contributor, among other threats. Many studies have demonstrated impacts of low doses of insecticides on insect behavior, but have not elucidated links to insecticidal activity at the molecular and cellular levels. Here, the histological, physiological, and behavioral impacts of imidacloprid are investigated in Drosophila melanogaster, an experimental organism exposed to insecticides in the field. We show that oxidative stress is a key factor in the mode of action of this insecticide at low doses. Imidacloprid produces an enduring flux of Ca2+ into neurons and a rapid increase in levels of reactive oxygen species (ROS) in the larval brain. It affects mitochondrial function, energy levels, the lipid environment, and transcriptomic profiles. Use of RNAi to induce ROS production in the brain recapitulates insecticide-induced phenotypes in the metabolic tissues, indicating that a signal from neurons is responsible. Chronic low level exposures in adults lead to mitochondrial dysfunction, severe damage to glial cells, and impaired vision. The potent antioxidant, N-acetylcysteine amide (NACA), reduces the severity of a number of the imidacloprid-induced phenotypes, indicating a causal role for oxidative stress. Given that other insecticides are known to generate oxidative stress, this research has wider implications. The systemic impairment of several key biological functions, including vision, reported here would reduce the resilience of insects facing other environmental challenges.

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Section: Imidacloprid Perturbs the Expression Of Genes Related To Stressmentioning

confidence: 66%

Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila

Martelli

Zuo

Wang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

107

112

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“…It is worth to note that the accumulation of damaged proteins is partly dependent on other ageing factors, as well. Mitochondrial DNA damages leads to dysfunctional mitochondrial and elevated levels of reactive oxygen species in the cell, leading to increased protein damage 38 . Vice-versa, the functionality of DNA repair proteins are shown to decline with age, leading to a higher occurrence of mutated DNA strands escaping from the repair mechanism 39,40 .…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of repair, resilience and retention of damage determine the conditions for replicative ageing

Borgqvist

Welkenhuysen

Cvijović

2020

Sci Rep

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Accumulation of damaged proteins is a hallmark of ageing, occurring in organisms ranging from bacteria and yeast to mammalian cells. During cell division in Saccharomyces cerevisiae, damaged proteins are retained within the mother cell, resulting in an ageing mother while a new daughter cell exhibits full replicative potential. The cell-specific features determining the ageing remain elusive. It has been suggested that the replicative ageing is dependent on the ability of the cell to repair and retain pre-existing damage. To deepen the understanding of how these factors influence the life of individual cells, we developed and experimentally validated a dynamic model of damage accumulation accounting for replicative ageing on the single cell level. The model includes five essential properties: cell growth, damage formation, damage repair, cell division and cell death, represented in a theoretical framework describing the conditions allowing for replicative ageing, starvation, immortality or clonal senescence. We introduce the resilience to damage, which can be interpreted as the difference in volume between an old and a young cell. We show that the capacity to retain damage deteriorates with high age, that asymmetric division allows for retention of damage, and that there is a trade-off between retention and the resilience property. Finally, we derive the maximal degree of asymmetry as a function of resilience, proposing that asymmetric cell division is beneficial with respect to replicative ageing as it increases the lifespan of a given organism. The proposed model contributes to a deeper understanding of the ageing process in eukaryotic organisms. Cell division, growth and death are fundamental features of any living organism. During its life cycle, a cell produces a set of functional components such as proteins or other metabolites, which will ultimately allow the cell to divide, giving rise to a newly born daughter cell. However, due to inherent imperfections in the cellular machinery over time, cells are slowly deteriorating causing essential intracellular functions to perish. At the very end of a cell's lifespan, age-associated damage builds up consistently impairing the ability of the cell to divide and survive, which eventually culminates in cell death. In environments with a sufficient amount of food, damage will be formed as a consequence of cell growth. This causes the partitioning of damage between the progenitor and progeny during cell division to be an important function. An asymmetric distribution of cell mass after division constitutes a vital part of ageing in the yeast Saccharomyces cerevisiae (S.cerevisiae). The number of divisions before cell death is a measure of the age of a single yeast cell, which has been studied substantially by means of experiments 1,2 , and it is called the replicative life span (RLS). The asymmetric division of the budding yeast results in a large ageing mother cell with a finite RLS and a new small daughter cell with full replicative potential 3. Replicative ageing in...

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“…Analogous findings have been observed for mtDNA mutations in complex III [ 86 ] and IV [ 87 ] in other human diseases. Aside from pathological variants, also common single nucleotide polymorphisms (SNPs) found in some haplogroups (i.e., the set of homoplasmic variants that define individuals with a common geographical origin) have been associated to an increased production of ROS, as shown for variants of haplogroups N and M [ 88 ].…”

Section: Mitochondrial Dna and Osmentioning

confidence: 99%

Oxidative Stress in Reproduction: A Mitochondrial Perspective

Almansa-Ordonez¹,

Bellido

Vassena³

et al. 2020

Biology

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Mitochondria are fundamental organelles in eukaryotic cells that provide ATP through oxidative phosphorylation. During this process, reactive oxygen species (ROS) are produced, and an imbalance in their concentrations can induce oxidative stress (OS), causing cellular damage. However, mitochondria and ROS play also an important role in cellular homeostasis through a variety of other signaling pathways not related to metabolic rates, highlighting the physiological relevance of mitochondria–ROS interactions. In reproduction, mitochondria follow a peculiar pattern of activation, especially in gametes, where they are relatively inactive during the initial phases of development, and become more active towards the final maturation stages. The reasons for the lower metabolic rates are attributed to the evolutionary advantage of keeping ROS levels low, thus avoiding cellular damage and apoptosis. In this review, we provide an overview on the interplay between mitochondrial metabolism and ROS during gametogenesis and embryogenesis, and how OS can influence these physiological processes. We also present the possible effects of assisted reproduction procedures on the levels of OS, and the latest techniques developed to select gametes and embryos based on their redox state. Finally, we evaluate the treatments developed to manage OS in assisted reproduction to improve the chances of pregnancy.

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Mitochondrial Genome (mtDNA) Mutations that Generate Reactive Oxygen Species

Cited by 109 publications

References 108 publications

Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila

Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila

Synergistic effects of repair, resilience and retention of damage determine the conditions for replicative ageing

Oxidative Stress in Reproduction: A Mitochondrial Perspective

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