The document discusses mitochondrial DNA (mtDNA) and its inheritance, highlighting that mtDNA is maternally inherited as paternal mtDNA is degraded during fertilization. It explains the structure and function of mitochondria, the endosymbiotic theory of their evolution, and the high mutation rates associated with mtDNA, which contribute to various mitochondrial diseases. Key diseases mentioned include Leber hereditary optic neuropathy, Kearns-Sayre syndrome, and MELAS, emphasizing the clinical implications of mtDNA mutations.

1. Mitochondrial DNA
Inheritance: A Journey into
the Heart of Our Cells
Heena V Mehta
Seminar Presentation

2. Mitochondria:
1. Found in both plants and animals
2. Double membrane structure.
3. Inner membrane.
4. Outer membrane.
5. Intermembrane space.
6. Matrix – innermost part - enzyme for TCA cycle.
7. Cristae – Folded structure.
8. Ribosome- Protein synthesis.
9. dsDNA (important) – multiple copies.
10. F0 – F1 complex – ATP synthase – Synthesize
ATP from ADP and inorganic Phosphate.
Let’s
Recall!!!
https://www.pinterest.com/pin/83738874297250623/

3. Mitochondria Evolution: The
Endosymbiotic Theory
• Lynn Margulis - evolutionary biologist
and author – endosymbiosis (1967)
• Explains how organelles in eukaryotic
cell originated from bacteria.
https://asm.org/articles/2024/june/beyond-endosymbiosis-discovering-first-nitroplast
https://en.wikipedia.org/wiki/Lynn_Margulis

4. Need proof!!!!
1. Structure - both mitochondria
and bacteria has kind of oval.
2. Size - 0.5 to 1 micrometer.
3. Circular DNA
4. Reproduction – binary fission
5. Ribosome –
Normally 70S – prokaryotes 80 –
eukaryotes
But mitochondrial ribosome is 70S
0.5 to 1 micrometer.
oval
Circular DNA
Binary fission in mitochondria
and prokaryotes
https://biologyreader.com/types-of-binary-fission.html
https://en.wikipedia.org/wiki/Mitochondrial_DNA

5. Mitochondrial DNA:
• Abbreviated as mtDNA
• Double stranded circular DNA
• There are several copies of dsDna in mitochondrion and there
are many mitochondria in each cell.
• There are no histones or any other protein associated with
mtDNA.
• The gene contain no introns
• High mutation rate
https://media.springernature.com/lw685/springer-static/image/chp
78-981-15-9364-2_16-1/MediaObjects/501338_0_En_16-1_Fig1_HT

6. Mitochondrial DNA
16.6 kilobases in size, dsDNA
encodes
37 Mitochondrial
gene
13 encode for polypeptides
involved in respiratory
chain.
24 22 tRNA
2 rRNA
Mitochondrial DNA:
https://jp.pinterest.com/pin/531002612292646025/?send=true

7. Mitochondrial DNA Inheritance:
Maternal or Paternal????
• During fertilization, only nucleus of sperm
enters the egg cell and fuses with eggs
nucleus.
• Therefore, Mitochondrial DNA is inherited
from one’s mother.
In any case if paternal mtDNA penetrates/ passes the egg it
gets diluted due to the presence of maternal mtDNA
Sperm mitochondria is degraded and eliminated in
most of the mammals by
 Autophagy – engulfment and degradation
 Ubiquitin system – targets and degrade
What happens to sperm
mitochondria then????
https://epgp.inflibnet.ac.in/epgpdata/uploads/epgp_content/S000016FS/P000700/M019161/E
T/1516259917FSC_P13_M8_e-text.pdf

8. Nuclear DNA Mitochondrial DNA

9. Homoplasmy and Heteroplasmy
Homoplasmy- All copies of the
mtDNA are identical, either all
normal or all abnormal (wild type or
mutant).
• Describe the state of mitochondrial DNA (mtDNA) in a cell or tissue.
• Heteroplasmy- mixture of two or more
mitochondrial genotypes.
• Many pathogenic mutation are
heteroplasmic – genetic mutation –
increase chances of disease or disorder.
- Wilde type
(normal)
- Mutant
(abnormal)
Key-
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psig=AOvVaw3OE6qayIs_QYwbno0ECF1L&ust=1732366210743000&source=images&cd=vfe&o
pi=89978449&ved=0CBQQjRxqFwoTCMim65z974kDFQAAAAAdAAAAABAE

10. Why mitochondrial DNA has high
mutation rate???
1.
Very high mutation rate (especially in D-loop) – 10 or 20
times higher than nuclear DNA.
Lack of protective histones.
2.
3.
Inefficient DNA repair systems.
4.
Continuous exposure to reactive
oxygen species (ROS).

11. Mitochondrial diseases:
1. Leber Hereditary Optic Neuropathy (LHON) –
- Caused by defect in the complex 1 (NADH dehydrogenase), leads- mitochondrial dysfunctioning and
oxidative damage.
- Symptom- vision loss.
- More males are affected than female.
2. Kearns-Sayre syndrome (KSS)-
- caused by deletions in mitochondrial DNA
- affects heart and eyes
3. MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)-
- caused by pathogenic variants in mitochondrial DNA (mtDNA)
- symptom- lactic acid accumulation in blood – leads to vomiting, abdominal pain, fatigue, muscle
weakness and difficulty breathing.

12. Reference:
•
https://www.nature.com/scitable/topicpage/mtdna-and-mitochondrial-diseases-903/#:~:text=As%20previ
ously%20mentioned%2C%20mitochondrial%20DNA,uncles%2C%20and%20other%20maternal%20relative
s.
• https://medlineplus.gov/genetics/chromosome/mitochondrial-dna/#:~:text=This%20genetic%20material
%20is%20known,essential%20for%20normal%20mitochondrial%20function.
• https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases
• https://www.youtube.com/watch?v=kyxF0cyyzTE&t=1131s
• https://www.youtube.com/watch?v=rg7GrJVEyek&t=792s

13. Thankyou!!!