scholarly journals Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division

2015 ◽  
Vol 25 (4) ◽  
pp. 706-714 ◽  
Author(s):  
Riikka Jokinen ◽  
Paula Marttinen ◽  
James B. Stewart ◽  
T. Neil Dear ◽  
Brendan J. Battersby
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Division ◽  
Tissue Specific ◽  
Dna Segregation

scholarly journals Gimap3 Regulates Tissue-Specific Mitochondrial DNA Segregation

PLoS Genetics ◽  
2010 ◽  
Vol 6 (10) ◽  
pp. e1001161 ◽  
Author(s):  
Riikka Jokinen ◽  
Paula Marttinen ◽  
Helen Katarin Sandell ◽  
Tuula Manninen ◽  
Heli Teerenhovi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Tissue Specific ◽  
Dna Segregation

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

scholarly journals Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Liya Wang ◽  
Ren Sun ◽  
Staffan Eriksson
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dna ◽  
Biochemical Characterization ◽  
Basic Knowledge ◽  
Rat Tissues ◽  
Nucleotide Synthesis ◽  
Tissue Specific ◽  
Mtdna Depletion ◽  
Adult Rat ◽  
Mitochondrial Dna Depletion

Abstract Background Deficiency in thymidine kinase 2 (TK2) or p53 inducible ribonucleotide reductase small subunit (p53R2) is associated with tissue specific mitochondrial DNA (mtDNA) depletion. To understand the mechanisms of the tissue specific mtDNA depletion we systematically studied key enzymes in dTMP synthesis in mitochondrial and cytosolic extracts prepared from adult rat tissues. Results In addition to mitochondrial TK2 a cytosolic isoform of TK2 was characterized, which showed similar substrate specificity to the mitochondrial TK2. Total TK activity was highest in spleen and lowest in skeletal muscle. Thymidylate synthase (TS) was detected in cytosols and its activity was high in spleen but low in other tissues. TS protein levels were high in heart, brain and skeletal muscle, which deviated from TS activity levels. The p53R2 proteins were at similar levels in all tissues except liver where it was ~ 6-fold lower. Our results strongly indicate that mitochondria in most tissues are capable of producing enough dTTP for mtDNA replication via mitochondrial TK2, but skeletal muscle mitochondria do not and are most likely dependent on both the salvage and de novo synthesis pathways. Conclusion These results provide important information concerning mechanisms for the tissue dependent variation of dTTP synthesis and explained why deficiency in TK2 or p53R2 leads to skeletal muscle dysfunctions. Furthermore, the presence of a putative cytosolic TK2-like enzyme may provide basic knowledge for the understanding of deoxynucleoside-based therapy for mitochondrial disorders.

Tissue-specific distribution of donor mitochondrial DNA in cloned mice produced by somatic cell nuclear transfer

genesis ◽  
2004 ◽  
Vol 39 (2) ◽  
pp. 79-83 ◽  
Author(s):  
Kimiko Inoue ◽  
Narumi Ogonuki ◽  
Yoshie Yamamoto ◽  
Kaoru Takano ◽  
Hiromi Miki ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Tissue Specific ◽  
Specific Distribution

scholarly journals Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria

2016 ◽  
Vol 113 (30) ◽  
pp. E4276-E4285 ◽  
Author(s):  
Gokhan Akman ◽  
Radha Desai ◽  
Laura J. Bailey ◽  
Takehiro Yasukawa ◽  
Ilaria Dalla Rosa ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Control Region ◽  
Mitochondrial Disease ◽  
Genetic Information ◽  
Disease Mechanism ◽  
Dna Segregation ◽  
D Loop ◽  
Mitochondrial Dna Replication ◽  
Pathological Variant ◽  
Potential Substrate

The genetic information in mammalian mitochondrial DNA is densely packed; there are no introns and only one sizeable noncoding, or control, region containing key cis-elements for its replication and expression. Many molecules of mitochondrial DNA bear a third strand of DNA, known as “7S DNA,” which forms a displacement (D-) loop in the control region. Here we show that many other molecules contain RNA as a third strand. The RNA of these R-loops maps to the control region of the mitochondrial DNA and is complementary to 7S DNA. Ribonuclease H1 is essential for mitochondrial DNA replication; it degrades RNA hybridized to DNA, so the R-loop is a potential substrate. In cells with a pathological variant of ribonuclease H1 associated with mitochondrial disease, R-loops are of low abundance, and there is mitochondrial DNA aggregation. These findings implicate ribonuclease H1 and RNA in the physical segregation of mitochondrial DNA, perturbation of which represents a previously unidentified disease mechanism.

Tissue-specific Distribution of Multiple Mitochondrial DNA Rearrangements during Human Aginga

1998 ◽  
Vol 854 (1 TOWARDS PROLO) ◽  
pp. 171-181 ◽  
Author(s):  
SERGEY A. KOVALENKO ◽  
GEORGE KOPSIDAS ◽  
JOANNE KELSO ◽  
FRANKLIN ROSENFELDT ◽  
ANTHONY W. LINNANE
Keyword(s):  
Mitochondrial Dna ◽  
Dna Rearrangements ◽  
Tissue Specific ◽  
Specific Distribution

Nuclear genetic control of mitochondrial DNA segregation

2003 ◽  
Vol 33 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Brendan J. Battersby ◽  
J.C. Loredo-Osti ◽  
Eric A. Shoubridge
Keyword(s):  
Mitochondrial Dna ◽  
Genetic Control ◽  
Dna Segregation

scholarly journals Mitochondrial DNA segregation in hematopoietic lineages does not depend on MHC presentation of mitochondrially encoded peptides

2005 ◽  
Vol 14 (17) ◽  
pp. 2587-2594 ◽  
Author(s):  
Brendan J. Battersby ◽  
Margaret E. Redpath ◽  
Eric A. Shoubridge
Keyword(s):  
Mitochondrial Dna ◽  
Dna Segregation ◽  
Mhc Presentation
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