Mitochondrial DNA - and diseases. .pptx

Mitochondrial DNA - and diseases

1. Mitochondrial DNA and diseases By Sagar sambhaji kokane

2. Mitochondria 90% of ATP generated there 10 to 1000s per cell (highest in brain, skeletal muscle, heart, kidney, liver) About 50 known mutations of human mitochondrial DNA Chapter 12 (pp. 349-354)

3. About 90 different proteins make up the Electron Transport Chain Figure 12.2

4. Endosymbiosis

5. Mitochondrial DNA …the “25 th chromosome”? 16,568 bp 2 Ribosomal RNAs 22 Transfer RNAs 13 Proteins 2-10 copies per organelle Figure 12.3

6. 13 of the 90 Electron Transport Chain proteins are encoded by mitochondrial DNA. The other 77 (plus about 1000 other mitochondrial proteins) are encoded by nuclear DNA. ...So, mitochondria truly are a cooperative venture between two genetic systems!

7. Mitochondrial Division

8. Sperm mitochondria destroyed once in egg cell…

9. Figure 12.4 Affected females have affected offspring Affected males don’t Called “Maternal Inheritance”

10. ≈ 100,000 mitochondria in an immature egg cell, but only 100 in a mature egg cell

11. Homoplasmy = Same mitochondrial genome in all tissues of a body. Heteroplasmy = More than one mitochondrial genome in a body, but can have various ratios in different tissues.

12. Homoplasmy = Same mitochondrial genome in all tissues of a body. Heteroplasmy = More than one mitochondrial genome in a body, but can have various ratios in different tissues. This one is more common !

13. If a mutation occurs in the mitochondrial DNA of the mother, the severity of the disease in the offspring depends on: Amount of mutant mitochondria inherited by child Partitioning of mutant mitochondria to different tissues of the body Energy needs of different tissues (higher in heart, muscle, brain, liver)

14. Mitochondrial Encephalomyopathy with Lactic Acidosis & Strokelike Episodes = ‘MELAS’ (pp. 355-357) Most common mitochondrial disease Recurrent strokes before age of 40 Myopathy (muscle weakening) Lower pH (due to lactic acid build-up) Deafness Droopy eyelids Short stature Diabetes

15. MELAS mutation is in the gene for the tRNA for Leucine 80% of mutations reduced protein synthesis shorter tRNA half-life no new proteins < See clumps of deformed mitochondria in arteries of brain….stroke?

16. Kearns-Sayre Syndrome = KSS (pp. 358-359) Ophthalmoplegia (paralysis or weakness of one or more eye muscles) Degeneration of pigment layer of retina Cardiac abnormalities Neurological abnormalities Onset at age 20 (fatal in few years) Large deletions (1000s bp) of mito DNA; duplications Is not typically inherited, but rather is ‘sporadic’ (meaning it just seems to show up in people)

17. Ophthalmoplegia

18. Mitochondrial DNA 16,568 bp Figure 12.3 ¼ of chromosome often deleted

19. Free-Radical “atom or molecule with an unpaired electron” They are very reactive.

20. Skin aging/wrinkling

21. Skin aging/wrinkling

22. What can you do to prevent Free-Radical damage ? Get your Vitamins-E and-C and β -Carotene (Vitamin-A precursor). These are ‘anti-oxidants’. Regular exercise. Although exercise generates free-radicals if you do it enough your body responds by absorbing them. Eat less. Lab rats on limited diets lived 50% longer, Fruitflies lived 30% longer. Reduce smoking, drinking alcohol, fatty foods Get less sun exposure.

23. Mitochondrial DNA 16,568 bp Figure 12.3 This region doesn’t code for anything

24. Mitochondria DNA can be used to study our past: Maternally inherited only No recombination Non-coding region collects mutations more quickly than nuclear DNA (less of a repair mechanism) Applications : Evolution & Forensics

25. Shot in 1882. Buried on his parent’s farm in Missouri.

26. 2000

27. DNA testing was done on the remains of a Vietnam soldier who was buried in the Tomb of the Unknowns at Arlington National Cemetery Remains of unidentified soldiers from WW I and WW II, Korea & Vietnam

28. In this case, they did RFLP analysis of DNA from the mitochondria. Extracted mito DNA from the buried bones and compared that to the DNA of the supposed mother and siblings

29. It matched those of United States Air Force First Lieutenant Michael Joseph Blassie. Lieutenant Blassie's remains were returned to his family in July 1998, and were buried in his hometown of St. Louis, Missouri. Remains of unidentified soldiers from WW I and WW II, Korea & Vietnam