scholarly journals Complete loss of mitofusins leads to gross respiratory chain dysfunction due to aberrant mitochondrial DNA maintenance and distribution

2016 ◽  
Vol 1857 ◽  
pp. e27
Author(s):  
Eduardo Silva Ramos ◽  
Elisa Motori ◽  
Christian Brüser ◽  
Inge Kühl ◽  
Benedetta Ruzzenente ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Respiratory Chain ◽  
Complete Loss ◽  
Dna Maintenance

A rapid assay for mitochondrial DNA damage and respiratory chain inhibition in the yeastSaccharomyces cerevisiae

2001 ◽  
Vol 38 (2-3) ◽  
pp. 153-158 ◽  
Author(s):  
Barry J. Barclay ◽  
Carrie L. DeHaan ◽  
Ursula G.G. Hennig ◽  
Oksana Iavorovska ◽  
Reid W. von Borstel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Respiratory Chain ◽  
Rapid Assay ◽  
Mitochondrial Dna Damage

scholarly journals Actin and myosin contribute to mammalian mitochondrial DNA maintenance

2011 ◽  
Vol 39 (12) ◽  
pp. 5098-5108 ◽  
Author(s):  
A. Reyes ◽  
J. He ◽  
C. C. Mao ◽  
L. J. Bailey ◽  
M. Di Re ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Dna Maintenance

scholarly journals Detecting respiratory chain deficiency in osteoblasts of older patients

2021 ◽  
Author(s):  
Daniel Hipps ◽  
Philip Dobson ◽  
Charlotte Warren ◽  
David McDonald ◽  
Andrew Fuller ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mouse Model ◽  
Respiratory Chain ◽  
Nuclear Genome ◽  
Mitochondrial Dna Mutation ◽  
Human Osteoblasts ◽  
Dna Mutation ◽  
Respiratory Chain Deficiency ◽  
Age Related ◽  
Cellular Dysfunction

Mitochondria contain their own genome which encodes 13 essential mitochondrial proteins and accumulates somatic variants at up to 10 times the rate of the nuclear genome. These mitochondrial genome variants lead to respiratory chain deficiency and cellular dysfunction. Work with the PolgAmut/PolgAmut mouse model, which has a high mitochondrial DNA mutation rate, showed enhanced levels of age related osteoporosis in affected mice along with respiratory chain deficiency in osteoblasts. To explore whether respiratory chain deficiency is also seen in human osteoblasts with age, we developed a protocol and analysis framework for imaging mass cytometry (IMC) in bone tissue sections to analyse osteoblasts in situ. We have demonstrated significant increases in complex I deficiency with age in human osteoblasts. This work is consistent with findings from the PolgAmut/PolgAmut mouse model and suggests that respiratory chain deficiency, as a consequence of the accumulation of age related mitochondrial DNA mutations, may have a significant role to play in the pathogenesis of human age related osteoporosis.

scholarly journals Heteroplasmic Point Mutations of Mitochondrial DNA Affecting Subunit I of Cytochrome c Oxidase in Two Patients With Acquired Idiopathic Sideroblastic Anemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4961-4972 ◽  
Author(s):  
Norbert Gattermann ◽  
Stefan Retzlaff ◽  
Yan-Ling Wang ◽  
Götz Hofhaus ◽  
Jürgen Heinisch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Ferric Iron ◽  
Point Mutations ◽  
Polymorphism Analysis ◽  
Sideroblastic Anemia ◽  
Wide Range

Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA (mtDNA), because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron (Fe3+) to ferrous iron (Fe2+). The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. It is not yet understood to which part of the respiratory chain the reduction of ferric iron is linked. In two patients with AISA we identified point mutations of mtDNA affecting the same transmembrane helix within subunit I of cytochrome c oxidase (COX I; ie, complex IV of the respiratory chain). The mutations were detected by restriction fragment length polymorphism analysis and temperature gradient gel electrophoresis. One of the mutations involves a T → C transition in nucleotide position 6742, causing an amino acid change from methionine to threonine. The other mutation is a T → C transition at nt 6721, changing isoleucine to threonine. Both amino acids are highly conserved in a wide range of species. Both mutations are heteroplasmic, ie, they establish a mixture of normal and mutated mitochondrial genomes, which is typical of disorders of mtDNA. The mutations were present in bone marrow and whole blood samples, in isolated platelets, and in granulocytes, but appeared to be absent from T and B lymphocytes purified by immunomagnetic bead separation. They were not detected in buccal mucosa cells obtained by mouthwashes and in cultured skin fibroblasts examined in one of the patients. In both patients, this pattern of involvement suggests that the mtDNA mutation occurred in a self-renewing bone marrow stem cell with myeloid determination. Identification of two point mutations with very similar location suggests that cytochrome c oxidase plays an important role in the pathogenesis of AISA. COX may be the physiologic site of iron reduction and transport through the inner mitochondrial membrane.

scholarly journals Exposure to environmental radionuclides alters mitochondrial DNA maintenance in a wild rodent

2020 ◽  
Vol 34 (2) ◽  
pp. 163-174 ◽  
Author(s):  
Jenni Kesäniemi ◽  
Anton Lavrinienko ◽  
Eugene Tukalenko ◽  
Ana Filipa Moutinho ◽  
Tapio Mappes ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Wild Rodent ◽  
Dna Maintenance ◽  
Environmental Radionuclides

scholarly journals Heteroplasmic Point Mutations of Mitochondrial DNA Affecting Subunit I of Cytochrome c Oxidase in Two Patients With Acquired Idiopathic Sideroblastic Anemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4961-4972 ◽  
Author(s):  
Norbert Gattermann ◽  
Stefan Retzlaff ◽  
Yan-Ling Wang ◽  
Götz Hofhaus ◽  
Jürgen Heinisch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Ferric Iron ◽  
Point Mutations ◽  
Polymorphism Analysis ◽  
Sideroblastic Anemia ◽  
Wide Range

Abstract Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA (mtDNA), because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron (Fe3+) to ferrous iron (Fe2+). The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. It is not yet understood to which part of the respiratory chain the reduction of ferric iron is linked. In two patients with AISA we identified point mutations of mtDNA affecting the same transmembrane helix within subunit I of cytochrome c oxidase (COX I; ie, complex IV of the respiratory chain). The mutations were detected by restriction fragment length polymorphism analysis and temperature gradient gel electrophoresis. One of the mutations involves a T → C transition in nucleotide position 6742, causing an amino acid change from methionine to threonine. The other mutation is a T → C transition at nt 6721, changing isoleucine to threonine. Both amino acids are highly conserved in a wide range of species. Both mutations are heteroplasmic, ie, they establish a mixture of normal and mutated mitochondrial genomes, which is typical of disorders of mtDNA. The mutations were present in bone marrow and whole blood samples, in isolated platelets, and in granulocytes, but appeared to be absent from T and B lymphocytes purified by immunomagnetic bead separation. They were not detected in buccal mucosa cells obtained by mouthwashes and in cultured skin fibroblasts examined in one of the patients. In both patients, this pattern of involvement suggests that the mtDNA mutation occurred in a self-renewing bone marrow stem cell with myeloid determination. Identification of two point mutations with very similar location suggests that cytochrome c oxidase plays an important role in the pathogenesis of AISA. COX may be the physiologic site of iron reduction and transport through the inner mitochondrial membrane.

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