Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders

Presentation slides 2017 16 Pages

Medicine - Human Genetics



- 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,


-Mitonchondrial DNA

-Matrix granules


-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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diagnosis treatment cure mitochondrial disorders




Title: Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders