Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders


Presentation slides, 2017
16 Pages, Grade: 1

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).

[Figure is omitted from this preview]

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

[Figure is omitted from this preview]

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).

[Figure is omitted from this preview]

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,

[Figure is omitted from this preview]

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).

[...]

Excerpt out of 16 pages

Details

Title
Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders
College
Egerton University
Grade
1
Author
Year
2017
Pages
16
Catalog Number
V381193
ISBN (eBook)
9783668575219
File size
3462 KB
Language
English
Tags
diagnosis, treatment, cure, mitochondrial, disorders
Quote paper
Patrick Kimuyu (Author), 2017, Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders, Munich, GRIN Verlag, https://www.grin.com/document/381193

Comments

  • No comments yet.
Read the ebook
Title: Diagnosis, Treatment, and Cure of Mitochondrial DNA Disorders


Upload papers

Your term paper / thesis:

- Publication as eBook and book
- High royalties for the sales
- Completely free - with ISBN
- It only takes five minutes
- Every paper finds readers

Publish now - it's free