Excerpt
INTRODUCTION
- Mitochondrial disorders seem to have become highly prevalent in the global population.
- From a pathological perspective, mitochondrial diseases comprises of an array of clinically heterogeneous diseases.
- According to Watts et al. (2014), mitochondrial mutations are inheritable and highly progressive.
- These disorders are attributable to mitochondrial DNA (mtDNA) mutations, and they are manifested by the lack of cellular energy.
- This pathological phenomenon has been found to be associated with defects in oxidative phosphorylation (OXPHOS).
- Since the first human pathological mtDNA mutations in 1988, over 250 mtDNA mutations which are linked to different pathological consequences have been identified.
- Therefore, this PowerPoint presentation provides a comprehensive overview of diagnosis,
Epidemiology of mitochondria disorders
- Epidemiological trends of mtDNA disorders indicate that the number of individuals with pathological mtDNA mutations has been increasing over the past few decades.
- This is attributable to the genetic implications of mtDNA disorders.
- For instance, it is reported that the US alone records approximately 4,000 children who are born with mtDNA disorders, annually.
- Overall, the prevalence of all mtDNA disorders is approximately 1:8500 individuals (Arpa et al., 2003).
- Additionally, it is reported that the incidence of mtDNA disorders among the US children is 1 per 4,000 children.
- Further epidemiological data indicate that the average number of births among women with transmissible mtDNA disease in the US is 800.
- Whereas, that of UK women is 150, annually (Gorman et al., 2015).
Mitochondria Structure and Function
- Mitochondria are double membrane semi-autonomous subcellular organelles.
- They exist in eukaryotic organisms, primarily in all nucleated mammalian cells.
- Their overall function is to generate ATP energy for cellular activities.
- As such, they serve as the powerhouses of the cells (Kühlbrandt, 2015).
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Anatomy of the Mitochondrion
Anatomically, mitochondria comprise of mitochondrial membranes and membrane compartments.
The main components are:
-The Outer membrane
-Intermembrane space,
-Lamellae
-Mitonchondrial DNA
-Matrix granules
-Ribosomes
-ATP synthase
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Membrane compartments
- The outer membrane encloses the inner membrane.
- It forms the boundary between the mitochondria and the cellular cytoplasm.
- The inner membrane separates the dense-central matrix from the inter-membrane space.
- It comprises of the inner boundary and the cristae which extends into the matrix.
- The cristae are considered as the primary sites of mitochondrial energy conversion (Alberts, 2014).
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Mitochondrial Genome
- The human mitochondrial DNA consists of 16,568 base pairs; thus, its molecular weight is 16568 bp.
- It is located in the mitochondria.
- Each mitochondrion bears 3 to 10 mtDNA molecules.
- Anatomically, an mtDNA is a doublestranded molecule comprising of a cytosinerich light (inner) strand and a guanine-rich heavy (outer) strand.
- Light strand transcription of mtDNA occurs clockwise, and it is initiated at OL.
- On the other hand, the transcription in the heavy strand occurs counterclockwise starting from the initiation point of the Dloop (HL) (Tuppen, Blakely,
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Differences between mtDNA and nuclear DNA
Both mitochondria and nuclear DNA share similarity in that they are double stranded genomic molecules. However, there are distinctive features between the two genomes ( Taylor & Turnbull, 2005 ).
Mitochondrial DNA
- mtDNA is circular in structure.
- It is small, made up of 16,569 base pairs.
- A cell contains thousands of mtDNA copies.
- Mitochondrial genome is not packaged into chromatin nor is it enveloped.
- Contains 3% of noncoding DNA sequences.
- Strictly maternal mode of inheritance.
Nuclear DNA
- Nuclear genome is linear in structure.
- It is large, made up of 3.3 billion base pairs.
- Only one copy of nuclear DNA exists in a cell.
- Nuclear genome is enveloped and packaged into chromatin.
- Contains 93% of noncoding DNA sequences.
- Equal inheritance
What causes mtDNA disorders?
- Mitochondrial disorders are attributable to mitochondrial DNA or nuclear DNA mutations (Koopman, Willems & Smeitink, 2012).
- These mutations may be acquired or inherited.
- Additionally, mtDNA dysfunctions due to environmental factors, pathogenic infections or drug-induced effects may underlie mtDNA abnormalities.
- Biologically, mutations in the nuclear DNA can be transferred to the mochondrion during segregation.
- As the cell divides, each daughter cell carries a single copy of mtDNA.
- In turn, each copy is duplicated into numerous copies, thus the lack of errorchecking capability of the mtDNA create chance for random mutations.
- It is reported that mtDNA has over 100-folds mutation rate than the nuclear DNA (Chial & Craig, 2008).
- This biological phenomenon is attributable to the proximity of mtDNA to the RC complexes within the mitochondrion.
- It also occurs due the exposure to ROS which are generated from oxidative reactions in the absence of protective histones and insufficient mtDNA repair mechanisms (Dianov et al., 2001).
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- Quote paper
- Patrick Kimuyu (Author), 2017, Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders, Munich, GRIN Verlag, https://www.grin.com/document/381193
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