Forms of extracellular mitochondria and their impact in health
Publication date: Available online 14 February 2019Source: MitochondrionAuthor(s): Sophia Miliotis, Bryan Nicolalde, Mayra Ortega, Jackie Yepez, Andrés CaicedoAbstractMitochondria play an important role as an intracellular energy plant and signaling organelle. However, mitochondria also exist outside cells where they could mediate cell-to-cell communication, repair and serve as an activator of the immune response. Their effects depend on the mitochondrial state or the form in which it is present, either as a whole functional structure as fragments or only as mitochondrial DNA. Herein, we provide evidence of why extr...
Source: Mitochondrion - February 14, 2019 Category: Biochemistry Source Type: research

Adult-onset Leigh syndrome linked to the novel stop codon mutation m.6579G>A in MT-CO1
We report a 17 year old female who presented with subacute encephalopathy, brainstem and extrapyramidal signs, raised CSF lactate, and symmetrical hyperintensities in the basal ganglia on T2-weighted cerebral MRI. The presence of cytochrome c oxidase deficient fibres in muscle tissue prompted sequencing of the entire mitochondrial genome which revealed the novel stop codon mutation m.6579G>A; p.Gly226X in MT-CO1. Here we present the case and review the clinicopathological and molecular spectrum of previously reported MT-CO1 truncating mutations. (Source: Mitochondrion)
Source: Mitochondrion - February 9, 2019 Category: Biochemistry Source Type: research

MtBrowse: An integrative genomics browser for human mitochondrial DNA
Publication date: Available online 7 February 2019Source: MitochondrionAuthor(s): Vipin Singh, Bani Jolly, Neeraj K. Rajput, Sayan Pramanik, Anshu BhardwajAbstractThe human mitochondrion is a unique semi-autonomous organelle with a genome of its own and also requires nuclear encoded components to carry out its functions. In addition to being the powerhouse of the cell, mitochondria plays a central role in several metabolic pathways. It is therefore challenging to delineate the cause-effect relationship in context of mitochondrial dysfunction. Several studies implicate mutations in mitochondrial DNA (mtDNA) in various compl...
Source: Mitochondrion - February 7, 2019 Category: Biochemistry Source Type: research

Biomarkers and clinical rating scales for sodium pyruvate therapy in patients with mitochondrial disease
Publication date: Available online 7 February 2019Source: MitochondrionAuthor(s): Yasutoshi Koga, Nataliya Povalko, Eisuke Inoue, Kazutaka Nashiki, Masashi TanakaAbstractBiomarkers and two clinical rating scales—the Japanese mitochondrial disease-rating scale (JMDRS) and Newcastle mitochondrial disease adult scale (NMDAS)—are clinically used when treating patients with mitochondrial disease. We explored the biomarker(s) and clinical rating scale(s) that are appropriate in preparing the protocol for a future clinical trial of sodium pyruvate (SP) therapy. A 48-week, prospective, single-centre, exploratory, clini...
Source: Mitochondrion - February 7, 2019 Category: Biochemistry Source Type: research

Withaferin A-mediated apoptosis in breast cancer cells is associated with alterations in mitochondrial dynamics
This study extends these observations to now demonstrate alterations in mitochondrial dynamics in WA-induced apoptosis. Assembly of complex III was decreased in MCF-7 and SUM159 cells but not in MDA-MB-231 as determined by native blue gel electrophoresis. Because WA is a Michael acceptor (electrophile), we explored the possibility of whether it covalently modifies cysteine residue(s) in ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 (UQCRFS1). Covalent modification of cysteine in UQCRFS1 was not observed after WA treatment. Instead, WA treatment inhibited chemically-induced mitochondrial fusion and decr...
Source: Mitochondrion - January 25, 2019 Category: Biochemistry Source Type: research

A zebrafish model to study small-fiber neuropathy reveals a potential role for GDAP1
Publication date: Available online 22 January 2019Source: MitochondrionAuthor(s): Ivo Eijkenboom, Jo M. Vanoevelen, Janneke G.J. Hoeijmakers, Iris Wijnen, Mike Gerards, Catharina G. Faber, Hubert J.M. SmeetsAbstractMutations in genes involved in mitochondrial dynamics (fusion and fission) have been implicated in many peripheral neuropathies. We hypothesized that defects in these genes could result in a phenotype resembling features of small-fiber neuropathy (SFN). This was investigated in zebrafish by knocking down two genes involved in mitochondrial dynamics gdap1 (possibly fission and motility) and opa1 (fusion) using es...
Source: Mitochondrion - January 22, 2019 Category: Biochemistry Source Type: research

The relevance of the supramolecular arrangements of the respiratory chain complexes in human diseases and aging
Publication date: Available online 18 January 2019Source: MitochondrionAuthor(s): I. Ramírez-Camacho, O. Flores-Herrera, C. ZazuetaAbstractMitochondrial dysfunction, a common factor in several diseases is accompanied with reactive oxygen species (ROS) production. These molecules react with proteins and lipids at their site of generation, establishing a vicious cycle which might result in further mitochondrial injury.It is well established that mitochondrial respiratory complexes can be organized into supramolecular structures called supercomplexes (SCs) or respirasomes; yet, the physiological/pathological relevance ...
Source: Mitochondrion - January 20, 2019 Category: Biochemistry Source Type: research

Mutation in Cytochrome B gene causes debility and adverse effects on health of sheep
Publication date: Available online 17 January 2019Source: MitochondrionAuthor(s): Aruna Pal, Abantika Pal, Samiddha Banerjee, S. Batobyal, P.N. ChatterjeeAbstractCytochrome B is the mitochondrial protein, which functions as part of the electron transport chain and is the main subunit of transmembrane cytochrome bc1 and b6f complexes affecting energy metabolism through oxidative phosphorylation. The present study was conducted to study the effect of mutation of Cytochrome B gene on the health condition of sheep, which the first report of association of mitochondrial gene with disease traits in livestock species. Non-synonym...
Source: Mitochondrion - January 18, 2019 Category: Biochemistry Source Type: research

Splitting the functions of Rim2, a mitochondrial iron/pyrimidine carrier
Publication date: Available online 18 January 2019Source: MitochondrionAuthor(s): Simon A.B. Knight, Heeyong Yoon, Ashutosh K. Pandey, Jayashree Pain, Debkumar Pain, Andrew DancisAbstractRim2 is an unusual mitochondrial carrier protein capable of transporting both iron and pyrimidine nucleotides. Here we characterize two point mutations generated in the predicted substrate-binding site, finding that they yield disparate effects on iron and pyrimidine transport. The Rim2 (E248A) mutant was deficient in mitochondrial iron transport activity. By contrast, the Rim2 (K299A) mutant specifically abrogated pyrimidine nucleotide tr...
Source: Mitochondrion - January 18, 2019 Category: Biochemistry Source Type: research

Hypoxia-reoxygenation of primary astrocytes results in a redistribution of mitochondrial size and mitophagy
The objective of this study is to assess astrocyte mitochondrial competence during hypoxia and post-hypoxia reoxygenation and to determine cellular adaptive and pathological changes in the mitochondrial network. We hypothesize that during metabolic distress in astrocytes; mitochondrial networks undergo a shift in fission-fusion dynamics that results in a change in the morphometric state of the entire mitochondrial network. This mitochondrial network shift may be protective during metabolic distress by priming mitochondrial size and facilitating mitophagy. We demonstrated that hypoxia and post-hypoxia reoxygenation of rat p...
Source: Mitochondrion - December 28, 2018 Category: Biochemistry Source Type: research

Editorial Board
Publication date: January 2019Source: Mitochondrion, Volume 44Author(s): (Source: Mitochondrion)
Source: Mitochondrion - December 28, 2018 Category: Biochemistry Source Type: research

Increased energetic demand supported by mitochondrial electron transfer chain and astrocyte assistance is essential to maintain the compensatory ability of the dopaminergic neurons in an animal model of early Parkinson's disease
Publication date: Available online 20 December 2018Source: MitochondrionAuthor(s): Katarzyna Kuter, Łukasz Olech, Norbert A. DencherAbstractPartial degeneration of dopaminergic neurons in the substantia nigra (SN), induces locomotor disability in animals but with time it is spontaneously compensated for by neurons surviving in the tissue by increasing their functional efficiency. Such compensation probably increases energy requirements and astrocyte support could be essential for this ability.We studied the effect of degeneration of dopaminergic neurons induced by the selective toxin 6-hydroxydopamine and/or death of 30% ...
Source: Mitochondrion - December 20, 2018 Category: Biochemistry Source Type: research

Circulating mitochondria DNA, a non-invasive cancer diagnostic biomarker candidate
Publication date: Available online 16 December 2018Source: MitochondrionAuthor(s): Justice Afrifa, Tie Zhao, Jingcui YuAbstractThe mitochondria are defined by their unique structure and cellular functions which includes energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, cell motility and transport as well as free radical generation. Recent advances geared towards enhancing the diagnostic and prognostic value of cancer patients have targeted the circulating mitochondria genome due to its specific and unique characteristics. Circulating mitochondria DNA is known to possess short leng...
Source: Mitochondrion - December 16, 2018 Category: Biochemistry Source Type: research

Temporal profile of serum mitochondrial DNA (mtDNA) in patients with aneurysmal subarachnoid hemorrhage (aSAH)
Publication date: Available online 5 December 2018Source: MitochondrionAuthor(s): Shafqat Rasul Chaudhry, Stilla Frede, Gerald Seifert, Thomas Mehari Kinfe, Mika Niemelä, Alf Lamprecht, Sajjad MuhammadAbstractAneurysmal subarachnoid hemorrhage (aSAH) is a highly complex disease. Majority of aSAH survivors confront post-SAH complications including cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) that mainly influence the clinical outcome. Tissue damage during early brain injury may lead to release of damage associated molecular pattern molecules (DAMPs) that may initiate and sustain inflammation during the ...
Source: Mitochondrion - December 6, 2018 Category: Biochemistry Source Type: research

Editorial Board
Publication date: November 2018Source: Mitochondrion, Volume 43Author(s): (Source: Mitochondrion)
Source: Mitochondrion - November 21, 2018 Category: Biochemistry Source Type: research

Calcium phosphate buffer formed in the mitochondrial matrix during preconditioning supports ΔpH formation and ischemic ATP production and prolongs cell survival –A hypothesis
Publication date: Available online 15 November 2018Source: MitochondrionAuthor(s): Krzysztof DolowyAbstractIschemic preconditioning makes cells less sensitive to oxygen deprivation. A similar effect can be achieved by increasing the calcium concentration and applying potassium channel openers. A hypothetical mechanism of preconditioning is presented. In the mitochondrial matrix, there is a calcium hydroxide buffer consisting of a few insoluble calcium phosphate minerals. During ischemia, calcium ions stored in the matrix buffer start to leak out, forming an electric potential difference, while hydroxyl ions remain in the m...
Source: Mitochondrion - November 16, 2018 Category: Biochemistry Source Type: research

The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort
Publication date: Available online 10 November 2018Source: MitochondrionAuthor(s): Piekutowska-Abramczuk Dorota, Kaliszewska Magdalena, Sułek Anna, Jurkowska Natalia, Ołtarzewski Mariusz, Jabłońska Ewa, Trubicka Joanna, Głowacka Aleksandra, Ciara Elżbieta, Kowalski Paweł, Langiewicz-Wojciechowska Karolina, Tesarova Marketa, Zeman Jiri, Kierdaszuk Biruta, Kuczyński Dariusz, Chmielewski Dariusz, Szymańska Edyta, Bakuła Agnieszka, Lusakowska Anna, Lipowska MartaAbstractDiseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecu...
Source: Mitochondrion - November 11, 2018 Category: Biochemistry Source Type: research

Assessment of associations between mitochondrial DNA haplogroups and attention deficit and hyperactivity disorder in Korean children
Publication date: Available online 10 November 2018Source: MitochondrionAuthor(s): In Wook Hwang, Bit Na Kwon, Hyung Jun Kim, Seung Hun Han, Noo Ri Lee, Myung Ho Lim, Ho Jang Kwon, Han Jun JinAbstractAttention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with multiple environmental and biological etiologies, including genetic factors. Until now, several genetic variants have been reported to be significantly associated with ADHD. Recently, the relationship between mitochondrial DNA (mtDNA) haplogroups and psychiatric disorders such as schizophrenia has also been reported. However, currently there are ...
Source: Mitochondrion - November 11, 2018 Category: Biochemistry Source Type: research

Mitochondrial dysfunction and gut microbiota imbalance: An intriguing relationship in chronic kidney disease
Publication date: Available online 5 November 2018Source: MitochondrionAuthor(s): Denise Mafra, Natália Alvarenga Borges, Bengt Lindholm, Peter Stenvinkel (Source: Mitochondrion)
Source: Mitochondrion - November 6, 2018 Category: Biochemistry Source Type: research

Mitochondrial dynamics, a key executioner in neurodegenerative diseases
Publication date: Available online 5 November 2018Source: MitochondrionAuthor(s): Komal Panchal, Anand Krishna TiwariAbstractNeurodegenerative diseases (NDs) are the group of disorder that includes brain, peripheral nerves, spinal cord and results in sensory and motor neuron dysfunction. Several studies have shown that mitochondrial dynamics and their axonal transport play a central role in most common NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS) etc. In normal physiological condition, there is a balance between mitochondrial fission and f...
Source: Mitochondrion - November 6, 2018 Category: Biochemistry Source Type: research

Mito-nuclear interactions modify Drosophila exercise performance
Publication date: Available online 6 November 2018Source: MitochondrionAuthor(s): Alyson Sujkowski, Adam N. Spierer, Thiviya Rajagopalan, Brian Bazzell, Maryam Safdar, Dinko Imsirovic, Robert Arking, David Rand, Robert WessellsAbstractEndurance exercise has received increasing attention as a broadly preventative measure against age-related disease and dysfunction. Improvement of mitochondrial quality by enhancement of mitochondrial turnover is thought to be among the important molecular mechanisms underpinning the benefits of exercise. Interactions between the mitochondrial and nuclear genomes are important components of t...
Source: Mitochondrion - November 6, 2018 Category: Biochemistry Source Type: research

Evidence that thiol group modification and reactive oxygen species are involved in hydrogen sulfide-induced mitochondrial permeability transition pore opening in rat cerebellum
We report here the effects of hydrogen sulfide (sulfide), that accumulates in ETHE1 deficiency, in rat cerebellum. Sulfide impaired electron transfer and oxidative phosphorylation. Sulfide also induced mitochondrial swelling, and decreased ΔΨm and calcium retention capacity in cerebellum mitochondria, which were prevented by cyclosporine A (CsA) plus ADP, and ruthenium red, suggesting mitochondrial permeability transition (mPT) induction. Melatonin (MEL) and N-ethylmaleimide also prevented sulfide-induced alterations. Prevention of sulfide-induced decrease of ΔΨm and viability by CsA and MEL was further...
Source: Mitochondrion - November 4, 2018 Category: Biochemistry Source Type: research

Peroxynitrite nitrates adenine nucleotide translocase and Voltage-Dependent Anion Channel 1 and alters their interactions and association with hexokinase II in mitochondria
In this study, we explored whether IR injury in isolated hearts induces tyrosine nitration of adenine nucleotide translocase (ANT) and alters its interaction with the voltage-dependent anion channel 1 (VDAC1). We found that IR injury induced tyrosine nitration of ANT and that exposure of isolated cardiac mitochondria to ONOO− induced ANT tyrosine, Y81, nitration. The exposure of isolated cardiac mitochondria to ONOO− also led ANT to form high molecular weight proteins and dissociation of ANT from VDAC1. We also found that IR injury in isolated hearts, hypoxic injury in H9c2 cells, and ONOO− treatment of H...
Source: Mitochondrion - November 2, 2018 Category: Biochemistry Source Type: research

Cardiac mitochondrial structure and function in tafazzin-knockdown mice
Publication date: Available online 30 October 2018Source: MitochondrionAuthor(s): Junhwan Kim, Kwangwon Lee, Hisashi Fujioka, Bernard Tandler, Charles L. HoppelAbstractMutations in the tafazzin gene are the basis of Barth syndrome. The tafazzin protein is responsible for the synthesis of cardiolipin. Doxycycline-induced tafazzin-knockdown mice have been used as a model for Barth syndrome. In the current study, we examined subsarcolemmal and interfibrillar mitochondria from hearts of tafazzin-knockdown mice, focusing on mitochondrial ultrastructure, oxidative phosphorylation, electron transport chain complex activity, and p...
Source: Mitochondrion - October 30, 2018 Category: Biochemistry Source Type: research

Detection of mitochondrial transfer RNA (mt-tRNA) gene mutations in patients with idiopathic pulmonary fibrosis and sarcoidosis
Publication date: Available online 26 October 2018Source: MitochondrionAuthor(s): Zoe Daniil, Ourania S. Kotsiou, Alexandros Grammatikopoulos, Sotiria Peletidou, Helen Gkika, Foteini Malli, Katerina Antoniou, Eirini Vasarmidi, Zissis Mamuris, Konstantinos Gourgoulianis, Emily ZifaAbstractMitochondrial reactive oxygen species production may lead to tissue injury associated with two respiratory disorders of unknown origin which are shared by common tissue fibrosis, IPF and sarcoidosis. Sequence analysis of 22 mt-tRNA genes and parts of their flanking genes revealed 32 and 45 mutations in 38/40 IPF and 69/85 sarcoidosis patie...
Source: Mitochondrion - October 27, 2018 Category: Biochemistry Source Type: research

A deafness-associated mitochondrial DNA mutation altered the tRNASer(UCN) metabolism and mitochondrial function
In this study, we investigated the pathogenic mechanism of deafness-associated 7505A > G variant in the mitochondrial tRNASer(UCN). The m.7505A > G variant affected the highly conserved adenine at position 11 (A11), disrupted the highly conserved A11-U24 base-pairing of DHU stem of tRNASer(UCN) and introduced a tertiary base pairing (G11-C56) with the C56 in the TΨC loop. We therefore hypothesized that the m.7505A > G variant altered both structure and function of tRNASer(UCN). We demonstrated that the m.7505A > G variant perturbed the conformation and stability of tRNASer(UCN), as indicated...
Source: Mitochondrion - October 16, 2018 Category: Biochemistry Source Type: research

Profiling of genomic alterations of mitochondrial DNA in gingivobuccal oral squamous cell carcinoma: Implications for disease progress
Publication date: Available online 24 September 2018Source: MitochondrionAuthor(s): Arindam Palodhi, Sahana Ghosh, Nidhan K. Biswas, Analabha Basu, Partha Pratim Majumder, Arindam Maitra, Arindam Maitra, Nidhan K. Biswas, Kishore Amin, Pradnya Kowtal, Shantanu Kumar, Subrata Das, Rajiv Sarin, Partha P. Majumder, I. Bagchi, B.B. Bairagya, A. Basu, M.K. Bhan, P. Chaturvedi, D. DasAbstractWe have identified 164 somatic mutations in mitochondrial DNA in gingivobuccal oral cancer by deep sequencing the mitochondrial genome from paired tumor and blood DNA samples from 89 patients. We have found evidence of positive selection of ...
Source: Mitochondrion - October 5, 2018 Category: Biochemistry Source Type: research

Development of a triplex Mtdna Qpcr assay to assess quantification, degradation, inhibition, and amplification target copy numbers
Publication date: Available online 25 September 2018Source: MitochondrionAuthor(s): Mark F. KavlickAbstractA hybrid absolute/relative qPCR assay which provides information regarding the condition of mitochondrial DNA (mtDNA) in a DNA sample is described. MtDNA concentration (copy number/μL) is determined via absolute quantification using a standard curve of a synthetic duplex DNA previously described (Kavlick, 2011). The state of mtDNA degradation is determined via the relative quantification of a mtDNA target found within the 16 s rRNA gene which is 3× longer than that of the short target in the former duplex a...
Source: Mitochondrion - October 5, 2018 Category: Biochemistry Source Type: research

Microglia polarization by mitochondrial metabolism modulation: A therapeutic opportunity in neurodegenerative diseases
Publication date: Available online 19 September 2018Source: MitochondrionAuthor(s): Arianna Di Stadio, Corrado Angelini (Source: Mitochondrion)
Source: Mitochondrion - September 20, 2018 Category: Biochemistry Source Type: research

Deep sequencing discovery of causal mtDNA mutations in a patient with unspecific neurological disease
In this study we have sequenced the mitochondrial genome of a girl with an unspecific neurological disorder and her mother. The later, while neurologically unaffected, suffers from a myopathy without clear cause. We were able to detect two non-synonymous mutations in the MT-ATP6 gene, which we propose are strong candidates for causative agents. 9017C as the main candidate present at high heteroplasmy frequency in the patient (83,2%) and moderate in the mother (45,4%) while it has a low frequency in the general population. It might act alone or in conjunction with 9010A as an accessory mutation. Evolutionary analysis showed...
Source: Mitochondrion - September 16, 2018 Category: Biochemistry Source Type: research

Frequency and association of mitochondrial genetic variants with neurological disorders
Publication date: Available online 13 September 2018Source: MitochondrionAuthor(s): Ana Carolina P. Cruz, Adriano Ferrasa, Alysson R. Muotri, Roberto H. HeraiAbstractMitochondria are small cytosolic organelles and the main source of energy production for the cells, especially in the brain. This organelle has its own genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can alter the normal energy metabolism in the brain, contributing to the development of a wide assortment of Neurological Disorders (ND), including neurodevelopmental syndromes, neurodegenerative diseases and neuropsychiatric disorders...
Source: Mitochondrion - September 13, 2018 Category: Biochemistry Source Type: research

Genetic analysis in a cohort of patients with hereditary optic neuropathies in Southwest of China
In conclusion, we reported the results of the molecular screening of 121 patients with hereditary optic neuropathies from southwest of China. Our results highlight the importance of investigating LHON-causing mtDNA mutations and OPA1 mutations in cases of suspected hereditary optic neuropathy. (Source: Mitochondrion)
Source: Mitochondrion - September 8, 2018 Category: Biochemistry Source Type: research

Whole exome sequencing identifies both nuclear and mitochondrial variations in an Iranian family with non-syndromic hearing loss
Publication date: Available online 8 September 2018Source: MitochondrionAuthor(s): Somayeh Khatami, Hassan Rokni-Zadeh, Neda Mohsen-Pour, Alireza Biglari, Majid Changi-Ashtiani, Mohammad Shahrooei, Tina ShahaniAbstractGenetic contributing factors to non-syndromic hearing loss (NSHL) are remarkably diverse spanning over autosomal to X-linked to mitochondrial inheritance patterns. Facing a quite unconventional pedigree, here we report implementation of whole exome sequencing (WES) to uncover mitochondrial pathogenic variant in a six-generation Iranian family with four cases affected with hereditary NSHL of variable severity....
Source: Mitochondrion - September 8, 2018 Category: Biochemistry Source Type: research

Mitochondrial dysfunction caused by m.2336T>C mutation with hypertrophic cardiomyopathy in cybrid cell lines
Publication date: Available online 6 September 2018Source: MitochondrionAuthor(s): Dan Li, Yaping Sun, Qianqian Zhuang, Yanrui Song, Bifeng Wu, Zexiao Jia, Huaye Pan, Hui Zhou, Shuangyi Hu, Bingtao Zhang, Yue Qiu, Yu Dai, Siyuan Chen, Xuejun Xu, Xufen Zhu, Aifu Lin, Wendong Huang, Zhong Liu, Qingfeng YanAbstractHypertrophic cardiomyopathy (HCM), affecting approximately 1 in 500 in the general population, is the most prominent cause of sudden heart disease-related mortality in the young. Mitochondrial DNA (mtDNA) mutations are among the primary causes of HCM. We previously identified a novel m.2336T>C homoplasmic mutatio...
Source: Mitochondrion - September 7, 2018 Category: Biochemistry Source Type: research

Comment on “establishment of human retinal mitoscriptome gene expression signature for diabetic retinopathy using cadaver eyes”
Publication date: Available online 5 September 2018Source: MitochondrionAuthor(s): Chenyu Li, Hong Luan, Xiaofei Man, Ping Gao, Yan XuAbstractWe read with great interest the article by Gowthaman and colleagues. The study's findings are useful for the discovery of biomarker and developing therapeutic regimen in diabetic retinopathy. On the other hand, from our perspective, the bioinformatics analyses need further context as the statistics for differential fold changes in expression data are not explained fully. Due to the high false positives caused by a large number of probes and multiple comparisons, it seems essential to...
Source: Mitochondrion - September 6, 2018 Category: Biochemistry Source Type: research

Meta-analysis of genotype-phenotype analysis of OPA1 mutations in autosomal dominant optic atrophy
Publication date: Available online 27 August 2018Source: MitochondrionAuthor(s): Michelle Ham, Julia Han, Kathryn Osann, Moyra Smith, Virginia KimonisAbstractAutosomal Dominant Optic Atrophy (ADOA) is a neuro-ophthalmic disease characterized by progressive bilateral vision loss, pallor of the optic disc, central vision loss, and impairment of color vision. Additionally, a small percentage of patients experience hearing loss and ataxia, while recent studies suggest disruption of cardiac and neuromuscular functions. In order to obtain a better understanding of the genotype-phenotype correlation of the various mutations in th...
Source: Mitochondrion - August 28, 2018 Category: Biochemistry Source Type: research

A mitochondrial DNA D loop insertion detected almost exclusively in non-replicating tissues with maternal inheritance across three generations
Publication date: Available online 13 August 2018Source: MitochondrionAuthor(s): Mehul A. Sharma, Ja Young J. Lee, Andrea Tam, Beheroze Sattha, Ian R. Mackenzie, Hilary D. Vallance, Sandra Sirrs, Fady Hannah-Shmouni, Hélène C.F. Côté, .Andre MattmanAbstractMuscle biopsy identified a possibly pathogenic, mitochondrial DNA D-loop insertion, in each of 5 family members from two generations, that was otherwise undetectable in most other tissues. The tissue specific regulation of heteroplasmy is reflected in an age related increase in muscle heteroplasmy level, across the pedigree. This latter finding...
Source: Mitochondrion - August 13, 2018 Category: Biochemistry Source Type: research

Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment
This study defines the healing cycle in metabolic terms and reframes the pathophysiology of chronic illness as the result of metabolic signaling abnormalities that block healing and cause the normal stages of the cell danger response (CDR) to persist abnormally. Once an injury occurs, active progress through the stages of healing is driven by sequential changes in cellular bioenergetics and the disposition of oxygen and carbon skeletons used for fuel, signaling, defense, repair, and recovery.>100 chronic illnesses can be organized into three persistent stages of the CDR. One hundred and two targetable chemosensory G-pro...
Source: Mitochondrion - August 10, 2018 Category: Biochemistry Source Type: research

Assessing mitochondrial heteroplasmy using next generation sequencing: A note of caution
Publication date: Available online 9 August 2018Source: MitochondrionAuthor(s): Mauro Santibanez Koref, Helen Griffin, Douglass M. Turnbull, Patrick F. Chinnery, Mary Herbert, Gavin HudsonAbstractThe mitochondrial genome has recently become the focus of several high-impact next-generation sequencing studies investigating the effect of mutations in disease and assessing the efficacy of mitochondrial replacement therapies.However, these studies have failed to take into consideration the capture of recurring translocations of mitochondrial DNA to the nuclear genome, known as nuclear mitochondrial sequences (NUMTs), continuing...
Source: Mitochondrion - August 9, 2018 Category: Biochemistry Source Type: research

Cell-free mitochondrial DNA in progressive multiple sclerosis
Publication date: Available online 8 August 2018Source: MitochondrionAuthor(s): Hannah Lowes, Angela Pyle, Martin Duddy, Gavin HudsonAbstractRecent studies have linked cell-free mitochondrial DNA (ccf-mtDNA) to neurodegeneration in both Alzheimer's and Parkinson's disease, raising the possibility that the same phenomenon could be seen in other diseases which manifest a neurodegenerative component. Here, we assessed the role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in end-stage progressive multiple sclerosis (PMS), where neurodegeneration is evident, contrasting both ventricular cerebral spinal fluid ccf-mtDNA...
Source: Mitochondrion - August 9, 2018 Category: Biochemistry Source Type: research

Combination of microdissection and single cell quantitative real-time PCR revealed intercellular mitochondrial DNA heterogeneities in fibroblasts of Kearns-Sayre syndrome patients
Publication date: Available online 6 August 2018Source: MitochondrionAuthor(s): Susann Kummer, Ekkehard WilichowskiAbstractKearns-Sayre syndrome (KSS) is a multisystemic disorder marked by aerobic cell metabolism dysfunction. Fibroblasts derived from KSS patient skin biopsy exhibit heterogeneous occurrence of mitochondrial genomes as those circular DNA molecules partially carry the common deletion. In our approach, we aim to evaluate the intercellular alterations in respect to mitochondrial DNA integrity by laser capture microdissection and multiplex quantitative real-time PCR in single cells. The obtained results give new...
Source: Mitochondrion - August 7, 2018 Category: Biochemistry Source Type: research

Toxic medications in Leber's hereditary optic neuropathy
This article reviews the evidence for medications with demonstrated and theoretical effects on mitochondrial function, specifically in relation to increased ROS production. The data reviewed provides guidance when selecting medications for individuals with LHON mutations (carriers) and are susceptible to conversion to affected. However, as with all medications, the proven benefits of these therapies must be weighed against, in some cases, purely theoretical risks for this unique patient population. (Source: Mitochondrion)
Source: Mitochondrion - August 4, 2018 Category: Biochemistry Source Type: research

Mitochondrial genomics in the cancer cell line encyclopedia and a scoring method to effectively pair cell lines for cytoplasmic hybridization
Publication date: Available online 31 July 2018Source: MitochondrionAuthor(s): S. Grandhi, L. Gould, J. Wang, A. Grandhi, T. LaFramboiseAbstractMitochondrial sequence variants have been associated with many human diseases, including cancer. A well-established experimental strategy to assess the impact of mitochondrial sequence variants is to generate cytoplasmic hybrids (cybrids). Cybridization facilitates the study of mitochondrial DNA (mtDNA) mutations under a controlled nuclear genetic background. However, in generating cybrids, it is important to select most suitable mtDNA donor and recipient cells so that any change i...
Source: Mitochondrion - August 2, 2018 Category: Biochemistry Source Type: research

Nuclear-Mitochondrial interactions influence susceptibility to HIV-associated neurocognitive impairment
Publication date: Available online 17 July 2018Source: MitochondrionAuthor(s): S. Smieszek, P. Jia, D.C. Samuels, Z. Zhao, J. Barnholtz-Sloan, H. Kaur, S. Letendre, R. Ellis, D.R. Franklin, T. Hulgan, A. Kallianpur, W.S. Bush, the CHARTER Study GroupAbstractHIV-associated neurocognitive impairment (NCI) is a term established to capture a wide spectrum of HIV related neurocognitive deficits ranging in severity from asymptomatic to dementia. The genetic underpinnings of this complex phenotype are incompletely understood. Mitochondrial function has long been thought to play a role in neurodegeneration, along with iron metabol...
Source: Mitochondrion - July 19, 2018 Category: Biochemistry Source Type: research

Chebulinic acid and Boeravinone B act as anti-aging and anti-apoptosis phyto-molecules during oxidative stress
ConclusionsCA and BB supplementation could significantly decrease oxidative stress, enhance cell viability and ultimately protected S. cerevisiae cells form aging. (Source: Mitochondrion)
Source: Mitochondrion - July 18, 2018 Category: Biochemistry Source Type: research

Genetic interactions influence susceptibility to HIV-associated neurocognitive impairment
Publication date: Available online 17 July 2018Source: MitochondrionAuthor(s): S. Smieszek, P. Jia, D.C. Samuels, Z. Zhao, J. Barnholtz-Sloan, H. Kaur, S. Letendre, R. Ellis, D.R. Franklin, T. Hulgan, A. Kallianpur, W.S. Bush, the CHARTER Study GroupAbstractHIV-associated neurocognitive impairment (NCI) is a term established to capture a wide spectrum of HIV related neurocognitive deficits ranging in severity from asymptomatic to dementia. The genetic underpinnings of this complex phenotype are incompletely understood. Mitochondrial function has long been thought to play a role in neurodegeneration, along with iron metabol...
Source: Mitochondrion - July 18, 2018 Category: Biochemistry Source Type: research

Muscle contractility of leg muscles in patients with mitochondrial myopathies
Publication date: Available online 11 July 2018Source: MitochondrionAuthor(s): Nanna Scharff Poulsen, Julia Rebecka Dahlqvist, Gitte Hedermann, Nicoline Løkken, John VissingAbstractBackgroundThe primary disease mechanism underlying mitochondrial myopathies (MM) is impaired energy generation to support muscle endurance. Little is known about muscle contractility before energy becomes deficient during muscle contractions. We investigated muscle contractility in MM to uncover potentially fixed weakness aspects of the disorders.MethodsContractility of calf and thigh muscles was investigated by comparing strength with co...
Source: Mitochondrion - July 12, 2018 Category: Biochemistry Source Type: research

Multichromosomal structure of the onion mitochondrial genome and a transcript analysis
Publication date: Available online 10 July 2018Source: MitochondrionAuthor(s): Mai Tsujimura, Takakazu Kaneko, Tomoaki Sakamoto, Seisuke Kimura, Masayoshi Shigyo, Hiroshi Yamagishi, Toru TerachiAbstractThe structures of plant mitochondrial genomes are more complex than those of animals. One of the reasons for this is that plant mitochondrial genomes typically have many long and short repeated sequences and intra- and intermolecular recombination may create various DNA molecules in this organelle. Recombination may sometimes create a novel gene that causes cytoplasmic male sterility (CMS).The onion has several cytoplasm typ...
Source: Mitochondrion - July 11, 2018 Category: Biochemistry Source Type: research

Proteome-wide prediction and annotation of mitochondrial and sub-mitochondrial proteins by incorporating domain information
Publication date: Available online 12 October 2017Source: MitochondrionAuthor(s): Ravindra Kumar, Bandana Kumari, Manish KumarAbstractMitochondrion is one of the most important subcellular organelle of eukaryotic cells. It carries out several biochemical functions that are extremely vital for cells. Defects in mitochondria also play an important role in the development and progression of different types of cancer. Therefore knowledge of complete mitochondrial protein repertoire is essential to understand overall mitochondrial functionality, maintenance, dynamics and metabolism. It would be of a great practical significance...
Source: Mitochondrion - July 11, 2018 Category: Biochemistry Source Type: research

Saccharomyces cerevisiae Mhr1 can bind Xho I-induced mitochondrial DNA double-strand breaks in vivo
Publication date: Available online 12 October 2017Source: MitochondrionAuthor(s): Kanchanjunga Prasai, Lucy C. Robinson, Kelly Tatchell, Lynn HarrisonAbstractMitochondrial DNA (mtDNA) double-strand break (DSB) repair is essential for maintaining mtDNA integrity, but little is known about the proteins involved in mtDNA DSB repair. Here, we utilize Saccharomyces cerevisiae as a eukaryotic model to identify proteins involved in mtDNA DSB repair. We show that Mhr1, a protein known to possess homologous DNA pairing activity in vitro, binds to mtDNA DSBs in vivo, indicating its involvement in mtDNA DSB repair. Our data also indi...
Source: Mitochondrion - July 11, 2018 Category: Biochemistry Source Type: research