Identification and functional characterization of mutations within HADHB associated with mitochondrial trifunctional protein deficiency
Publication date: Available online 12 September 2019Source: MitochondrionAuthor(s): Zhi-Rong Liu, Hai-Lin Dong, Yin Ma, Zhi-Ying WuAbstractMitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder with several phenotypes. Neuromyopathic form of MTP deficiency is characterized by infantile or juvenile-onset, progressive peripheral neuropathy and rhabdomyolysis. To date, only one Chinese patient harboring homozygous c. 739C>T (p.R247C) in HADHB has been reported. Here, using whole exome sequencing (WES), we identified a compound heterozygote of c.407T>C (p.M136T) and c.421G>A (p.A141T) withi...
Source: Mitochondrion - September 13, 2019 Category: Biochemistry Source Type: research
Genotypes of chronic progressive external ophthalmoplegia in a large adult-onset cohort
Publication date: Available online 12 September 2019Source: MitochondrionAuthor(s): Julia N. Heighton, Lauren I. Brady, Bekim Sadikovic, Dennis E. Bulman, Mark A. TarnopolskyAbstractChronic progressive external ophthalmoplegia (CPEO) is a common presentation of mitochondrial disease. We performed a retrospective evaluation of the molecular genetic testing and genotype-phenotype correlations in a large cohort of adult-onset CPEO patients (N = 111). One hundred percent of patients had at least one mitochondrial DNA (mtDNA) deletion. Genetic testing of nuclear genes encoding mitochondrial proteins identified pathogenic/li...
Source: Mitochondrion - September 13, 2019 Category: Biochemistry Source Type: research
SkQThy, a novel and promising mitochondria-targeted antioxidant
Publication date: Available online 6 September 2019Source: MitochondrionAuthor(s): T.N. Goleva, A.G. Rogov, G.A. Korshunova, T.A. Trendeleva, D.V. Mamaev, D.A. Aliverdieva, R.A. ZvyagilskayaAbstractSince thymoquinone (2-isopropyl-5-methylbenzoquinone) isolation from Nigella sativa in 1963, various studies have reported on its diverse pharmacological properties. However, despite its versatile healing abilities, clinical trials involving the use of thymoquinone have not been initiated due to its poor bioavailability. Many attempts have been made to improve the therapeutic efficacy of thymoquinone by synthesizing analogs, as ...
Source: Mitochondrion - September 7, 2019 Category: Biochemistry Source Type: research
Editorial Board
Publication date: September 2019Source: Mitochondrion, Volume 48Author(s): (Source: Mitochondrion)
Source: Mitochondrion - September 6, 2019 Category: Biochemistry Source Type: research
Germline knockdown of spargel (PGC-1) produces embryonic lethality in Drosophila
Publication date: Available online 29 August 2019Source: MitochondrionAuthor(s): Jack George, Howard T. JacobsAbstractThe PGC-1 transcriptional coactivators have been proposed as master regulators of mitochondrial biogenesis and energy metabolism. Here we show that the single member of the family in Drosophila, spargel (srl) has an essential role in early development. Female germline-specific RNAi knockdown resulted in embryonic semilethality. Embryos were small, with most suffering a catastrophic derangement of cellularization and gastrulation, although genes dependent on localized determinants were expressed normally. Th...
Source: Mitochondrion - August 30, 2019 Category: Biochemistry Source Type: research
Targeted mitochondrial delivery of antisense RNA-containing nanoparticles by a MITO-Porter for safe and efficient mitochondrial gene silencing
Publication date: Available online 28 August 2019Source: MitochondrionAuthor(s): Eriko Kawamura, Mitsue Hibino, Hideyoshi Harashima, Yuma YamadaAbstractMitochondrial gene therapy will be needed to treat mitochondrial diseases. We previously demonstrated mitochondrial gene silencing by the mitochondrial delivery of antisense RNA oligonucleotide (ASO) targeting mtDNA-encoded mRNA using a MITO-Porter, a liposomal nano carrier system designed for mitochondrial delivery. Here, we report on the efficient packaging of ASO in the MITO-Porter via a nanoparticle packaging method, which showed a 10-fold higher packaging efficiency th...
Source: Mitochondrion - August 29, 2019 Category: Biochemistry Source Type: research
Amino and carboxy-terminal extensions of yeast mitochondrial DNA polymerase assemble both the polymerization and exonuclease active sites
Publication date: Available online 21 August 2019Source: MitochondrionAuthor(s): Carlos H. Trasviña-Arenas, Nallely Hoyos-Gonzalez, Atzimba Y. Castro-Lara, Annia Rodriguez-Hernandez, María E. Sanchez-Sandoval, Pedro Jimenez-Sandoval, Víctor M. Ayala-García, Corina Díaz-Quezada, Tiziana Lodi, Enrico Baruffini, Luis G. BriebaAbstractHuman and yeast mitochondrial DNA polymerases (DNAPs), POLG and Mip1, are related by evolution to bacteriophage DNAPs. However, mitochondrial DNAPs contain unique amino and carboxyl-terminal extensions that physically interact. Here we describe that N-terminal deletions in Mip1 polymerases a...
Source: Mitochondrion - August 21, 2019 Category: Biochemistry Source Type: research
Homozygous R627W mutations in POLG cause mitochondrial DNA depletion leading to encephalopathy, seizures and stroke-like episodes
Publication date: Available online 16 August 2019Source: MitochondrionAuthor(s): Arumugam Paramasivam, Challa Venkatapathi, Gampa Sandeep, Angamuthu K. Meena, Megha S. Uppin, Swati Mohapatra, Robert D.S. Pitceathly, Kumarasamy ThangarajAbstractMutations in the mitochondrial DNA maintenance gene POLG (DNA Polymerase Gamma, Catalytic Subunit), encoding mitochondrial DNA polymerase gamma (pol γ), are associated with an extremely broad phenotypic spectrum. We identified homozygous POLG c.1879C>T; p.R627W mutations in two siblings from a consanguineous South Asian family following targeted resequencing of 75 nuclear-encoded mi...
Source: Mitochondrion - August 17, 2019 Category: Biochemistry Source Type: research
Limited predictive value of TFAM in mitochondrial biogenesis
Publication date: Available online 13 August 2019Source: MitochondrionAuthor(s): Natalya Kozhukhar, Mikhail F. AlexeyevAbstractMitochondrial transcription factor A (TFAM) plays an important role in mitochondrial DNA (mtDNA) transcription and replication. In some experimental settings, TFAM expression parallels parameters of mitochondrial biogenesis, which led to a widespread acceptance of TFAM as marker of mitochondrial biogenesis. We modulated TFAM expression in several experimental systems and observed that it fails to consistently parallel mtDNA copy number and expression of mtDNA-encoded polypeptides. We suggest that t...
Source: Mitochondrion - August 14, 2019 Category: Biochemistry Source Type: research
Reversible dimerization of cytochrome c oxidase regulates mitochondrial respiration
Publication date: Available online 13 August 2019Source: MitochondrionAuthor(s): Rabia Ramzan, Annika Rhiel, Petra Weber, Bernhard Kadenbach, Sebastian VogtAbstractAlmost all energy consumed by higher organisms, either in the form of ATP or heat, is produced in mitochondria by respiration and oxidative phosphorylation through five protein complexes in the inner membrane. High-resolution x-ray analysis of crystallized cytochrome c oxidase (CytOx), the final oxygen-accepting complex of the respiratory chain, isolated by using cholate as detergent, revealed a dimeric structure with 13 subunits in each monomer. In contrast, Cy...
Source: Mitochondrion - August 14, 2019 Category: Biochemistry Source Type: research
Sorting out how Msp1 maintains mitochondrial membrane proteostasis
Publication date: Available online 5 August 2019Source: MitochondrionAuthor(s): Heidi L. Fresenius, Matthew L. WohleverAbstractRobust membrane proteostasis networks are essential for cells to withstand proteotoxic stress arising from environmental insult and intrinsic errors in protein production (Labbadia and Morimoto, 2015; Hegde and Zavodszky, 2019). Failures in mitochondrial membrane proteostasis are associated with cancer, aging, and a range of cardiovascular and neurodegenerative diseases (Wallace et al., 2010; Martin, 2012; Gustafsson and Gottlieb, 2007). As a result, mitochondria possess numerous pathways to mainta...
Source: Mitochondrion - August 6, 2019 Category: Biochemistry Source Type: research
Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation
Publication date: November 2019Source: Mitochondrion, Volume 49Author(s): Ina Katrine Nitschke Pettersen, Deusdedit Tusubira, Hanan Ashrafi, Sissel Elisabeth Dyrstad, Lena Hansen, Xiao-Zheng Liu, Linn Iren Hodneland Nilsson, Nils Gunnar Løvsletten, Kjetil Berge, Hege Wergedahl, Bodil Bjørndal, Øystein Fluge, Ove Bruland, Arild Christian Rustan, Nils Halberg, Gro Vatne Røsland, Rolf Kristian Berge, Karl Johan TronstadAbstractFatty acid oxidation is a central fueling pathway for mitochondrial ATP production. Regulation occurs through multiple nutrient- and energy-sensitive molecular mechanisms. We explored if upregulated...
Source: Mitochondrion - August 4, 2019 Category: Biochemistry Source Type: research
Mitogenome analysis of Indian isolate of Rhipicephalus microplus clade A sensu (Burger et al., 2014): A first report from Maritime South-East Asia
Publication date: Available online 2 August 2019Source: MitochondrionAuthor(s): Arun Kumar De, Ramachandran Muthiyan, Perumal Ponraj, K. Muniswamy, Jai Sunder, A. Kundu, D. Karunakaran, Zachariah George, M.S. Kundu, S.K. Zamir Ahmed, Dhruba Malakar, D. BhattacharyaAbstractThis communication reports a comprehensive profile of mitogenome analysis of Rhipicephalus microplus, isolated and identified from Andaman and Nicobar islands, a part of Maritime South East Asia. Complete mitogenome of Indian isolate of R. microplus (MK234703) was 14,903 bp. Mitochondrial (mt.) genome had 13 protein coding genes (PCGs), 22 tRNAs, two ri...
Source: Mitochondrion - August 3, 2019 Category: Biochemistry Source Type: research
Mitochondrial AAA proteases: A stairway to degradation
Publication date: Available online 1 August 2019Source: MitochondrionAuthor(s): Tyler E. Steele, Steven E. GlynnAbstractMitochondrial protein quality control requires the action of proteases to remove damaged or unnecessary proteins and perform key regulatory cleavage events. Important components of the quality control network are the mitochondrial AAA proteases, which capture energy from ATP hydrolysis to destabilize and degrade protein substrates on both sides of the inner membrane. Dysfunction of these proteases leads to the breakdown of mitochondrial proteostasis and is linked to the development of severe human disease...
Source: Mitochondrion - August 3, 2019 Category: Biochemistry Source Type: research
Activities of mitochondrial respiratory chain complexes in platelets of patients with Alzheimer's disease and depressive disorder
Publication date: Available online 1 August 2019Source: MitochondrionAuthor(s): Zdeněk Fišar, Hana Hansíková, Jana Křížová, Roman Jirák, Eva Kitzlerová, Martina Zvěřová, Jana Hroudová, László Wenchich, Jiří Zeman, Jiří RabochAbstractWe analyzed activities of complex I, II, III, and IV, and citrate synthase (CS) in patients with major depressive disorder (MDD) or Alzheimer's disease (AD) presenting with or without depression. Associations of these parameters with disease or disease severity were observed in both AD and MDD; however, mean values of mitochondrial parameters were significantly altered in AD...
Source: Mitochondrion - August 3, 2019 Category: Biochemistry Source Type: research
