The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

Boguszewska, Karolina; Szewczuk, Michał; Kaźmierczak-Barańska, Julia; Karwowski, Bolesław T.

doi:10.3390/molecules25122857

Cited by 59 publications

(41 citation statements)

References 214 publications

(359 reference statements)

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“…Beyond this, its role in the regulation of the cell cycle, cell growth and apoptosis is also reported [5,6]. Along with chloroplasts, mitochondria emerged from bacterial ancestors, and through evolution, retained specialized structures and haploid genomes [7]. Much of their genetic content is included in the nuclear genome, but a significant part remains in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

et al. 2021

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A mitochondrion is a cellular organelle able to produce cellular energy in the form of adenosine triphosphate (ATP). As in the nucleus, mitochondria contain their own genome: the mitochondrial DNA (mtDNA). This genome is particularly susceptible to mutations that are at the basis of a multitude of disorders, especially those affecting the heart, the central nervous system and muscles. Conventional clinical practice applied to mitochondrial diseases is very limited and ineffective; a clear need for innovative therapies is demonstrated. Gene therapy seems to be a promising approach. The use of mitochondrial DNA as a therapeutic, optimized by peptide-based complexes with mitochondrial targeting, can be seen as a powerful tool in the reestablishment of normal mitochondrial function. In line with this requirement, in this work and for the first time, a mitochondrial-targeting sequence (MTS) has been incorporated into previously researched peptides, to confer on them a targeting ability. These peptides were then considered to complex a plasmid DNA (pDNA) which contains the mitochondrial gene ND1 (mitochondrially encoded NADH dehydrogenase 1 protein), aiming at the formation of peptide-based nanoparticles. Currently, the ND1 plasmid is one of the most advanced bioengineered vectors for conducting research on mitochondrial gene expression. The formed complexes were characterized in terms of pDNA complexation capacity, morphology, size, surface charge and cytotoxic profile. These data revealed that the developed carriers possess suitable properties for pDNA delivery. Furthermore, in vitro studies illustrated the mitochondrial targeting ability of the novel peptide/pDNA complexes. A comparison between the different complexes revealed the most promising ones that complex pDNA and target mitochondria. This may contribute to the optimization of peptide-based non-viral systems to target mitochondria, instigating progress in mitochondrial gene therapy.

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Section: Introductionmentioning

confidence: 99%

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

et al. 2021

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“…The canonical-NHEJ (c-NHEJ) pathway is undetectable but microhomology-mediated end joining (MMEJ) may perform some DSB repair in mtDNA [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. A recent review [ 65 ] confirms that the repair systems of BER, MMR and NHEJ are operating in human cell mitochondria. However, the involvement of HR in the repair of DSBs in mtDNA is still questioned.…”

Section: Mitochondria Structure and Function In Normal And Cancer Cellsmentioning

confidence: 94%

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

Averbeck

Rodriguez-Lafrasse

2021

IJMS

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Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

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“…Mitochondrial DNA (mtDNA) is more susceptible to the adverse effects of reactive oxygen species (ROS) produced during oxidative phosphorylation than nuclear DNA [15]. Thus, BER is considered to be the main repair pathway for DNA damage in mitochondria [16,17]. NER (Figure 2a) is a central DNA repair pathway and a highly dynamic process responsible for removing bulky lesions from the genome [18][19][20].…”

Section: Major Dna Repair Pathways and Their Roles In Neurons And Microgliamentioning

confidence: 99%

DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease

Wang

Lautrup

Caponio

et al. 2021

IJMS

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DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

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The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

Cited by 59 publications

References 214 publications

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease

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