Stable heteroplasmy but differential inheritance of a large mitochondrial DNA deletion in nematodes

2002 ◽  
Vol 80 (5) ◽  
pp. 645-654 ◽  
Author(s):  
William Y Tsang ◽  
Bernard D Lemire
Keyword(s):  
Mitochondrial Dna ◽  
Caenorhabditis Elegans ◽  
Copy Number ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Mtdna Copy Number ◽  
Mitochondrial Dna Deletion ◽  
Dna Deletion ◽  
Average Proportion ◽  
Mtdna Deletion

Many human mitochondrial diseases are associated with defects in the mitochondrial DNA (mtDNA). Mutated and wild-type forms of mtDNA often coexist in the same cell in a state called heteroplasmy. Here, we report the isolation of a Caenorhabditis elegans strain bearing the 3.1-kb uaDf5 deletion that removes 11 genes from the mtDNA. The uaDf5 deletion is maternally transmitted and has been maintained for at least 100 generations in a stable heteroplasmic state in which it accounts for ~60% of the mtDNA content of each developmental stage. Heteroplasmy levels vary between individual animals (from ~20 to 80%), but no observable phenotype is detected. The total mtDNA copy number in the uaDf5 mutant is approximately twice that of the wild type. The maternal transmission of the uaDf5 mtDNA is controlled by at least two competing processes: one process promotes the increase in the average proportion of uaDf5 mtDNA in the offspring, while the second promotes a decrease. These two forces prevent the segregation of the mtDNAs to homoplasmy.Key words: mtDNA deletion, Caenorhabditis elegans, heteroplasmy, inheritance, mtDNA copy number.

scholarly journals Mechanisms of replication and repair in mitochondrial DNA deletion formation

2020 ◽  
Vol 48 (20) ◽  
pp. 11244-11258
Author(s):  
Gabriele A Fontana ◽  
Hailey L Gahlon
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Mitochondrial Dna Deletion ◽  
Deletion Formation ◽  
Dna Deletion ◽  
Mtdna Deletions ◽  
Mtdna Deletion

Abstract Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.

Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats

1992 ◽  
Vol 275 (3-6) ◽  
pp. 181-193 ◽  
Author(s):  
M.N. Gadaleta ◽  
G. Rainaldi ◽  
A.M.S. Lezza ◽  
F. Milella ◽  
F. Fracasso ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Dna Copy Number ◽  
Mitochondrial Dna Deletion ◽  
Dna Deletion ◽  
Mitochondrial Dna Copy Number

scholarly journals Muscle Mitochondrial DNA Copy Number, Deletion Mutation Frequency, and Physical Performance in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 889-889
Author(s):  
Jonathan Wanagat ◽  
Allen Herbst ◽  
Steven Prior ◽  
Judd Aiken ◽  
Debbie McKenzie ◽  
...  
Keyword(s):  
Older Adults ◽  
Mitochondrial Dna ◽  
Physical Performance ◽  
Performance Measures ◽  
Copy Number ◽  
Mutation Frequency ◽  
Deletion Mutation ◽  
Mtdna Copy Number ◽  
Mtdna Deletion ◽  
Deletion Frequency

Abstract Mitochondrial DNA (mtDNA) quantity and quality influence hallmarks of aging – mitochondrial dysfunction and genomic instability. The interactions between mtDNA quantity and quality and physical performance have not been extensively examined in humans. The aim of this study was to test the interactions between skeletal muscle mtDNA copy number, mtDNA deletion mutation frequency, and physical performance measures in older adults. Total DNA was isolated from muscle biopsies and used for quantitation of mtDNA copy number and mutation frequency by digital PCR. The biopsies were obtained from a cross-sectional cohort of 53 adults aged 50 to 86 years. Before the biopsy, physical performance measures were collected. MtDNA deletions increased exponentially with advancing age. On average, mtDNA deletion frequency increased 18-fold between 50 and 80, with a trend toward lower deletion frequency in females. MtDNA deletion frequency predicted declines in VO2 max, where 4.7% of the variation in VO2 max was explained by mtDNA deletion frequency. MtDNA copy number was negatively correlated with age and mtDNA deletion frequency, but positively correlated with lean mass. There was a trend to lower mtDNA deletion frequency in females, consistent with increased longevity in females. Larger studies may better delineate sex effects. These data are consistent with a role for mitochondrial function and genome integrity in the maintenance of physical performance with age. Analyses of mtDNA quality and quantity in longitudinal studies could extend our understanding of the importance of mitochondria in human aging and longevity.

scholarly journals Accurate Measurement of Mitochondrial DNA Deletion Level and Copy Number Differences in Human Skeletal Muscle

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e114462 ◽  
Author(s):  
John P. Grady ◽  
Julie L. Murphy ◽  
Emma L. Blakely ◽  
Ronald G. Haller ◽  
Robert W. Taylor ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Human Skeletal Muscle ◽  
Mitochondrial Dna Deletion ◽  
Dna Deletion

Sudden bilateral hearing loss and sporadic mitochondrial DNA deletion

2001 ◽  
Vol 115 (2) ◽  
pp. 128-131 ◽  
Author(s):  
Stefano Berrettini ◽  
Francesca Forli ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Hearing Loss ◽  
Mitochondrial Dna ◽  
Lactic Acid ◽  
Unknown Origin ◽  
Adult Onset ◽  
Mitochondrial Dna Deletion ◽  
Mtdna Mutations ◽  
Dna Deletion ◽  
Mtdna Deletion ◽  
Rest And Exercise

Abstract Several studies have indicated that a number of different mitochondrial DNA (mtDNA) mutations may be responsible for human pathologies. Sensorineural Hearing Loss (SNHL) may be associated with known syndromes (syndromal SNHL) or represent the only manifestation of mitochondrial damage (non-syndromal hearing loss). Moreover, mtDNA alterations may be responsible for aminoglycoside-induced deafness.We describe a patient harbouring a single sporadic mtDNA deletion, who presented with sudden adult-onset bilateral, although non-simultaneous SNHL, that was partially responsive to corticosteroids. Increased values of rest, and exercise, blood lactic acid were decisive for diagnosis, prompting muscle biopsy that revealed the mtDNA deletion. The case underscores the importance of investigating a mitochondrial disease in cases of SNHL of unknown origin and points out the importance of an increased blood level of lactic acid as a screening test.

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