* ONMITOCHONDRIA

PRESENTATION

*BY

*VARSHA GAITONDE

*What is a Mitochondrion?

*A cellular organelle probably of endosymbiotic origin that resides in the cytosol of most nucleated (eurkaryotic) cells.

* This organelle produces energy by oxidising organic acids and fats with oxygen by the process of oxidative phosphorylation and generates oxygen radicals (reactive oxygen species ROS )as a toxic by-product

*HISTORY

*Kallikar(1850) was first to describe muscle mito which he called Sarcosome.

*Altman called them Bioblasts

*Flemming (1882)coined the word filia for them

*Benda(1897) introduced the term Mitochondrion to designate thread like granules

* Mitochondrial Structure (cont.)

*Mitochondrial Genetics

* Each cell contains many mitochondria, each of which contains multiple copies of 16.5-k-b circular DNA molecule

*The mitochondrial genome is subject to a number of peculiarities of inheritance

* The nuclear and Mitochondrial genetic codes are similar but not identical

Outer membrane: • The outer mitochondrial membrane, which encloses the

entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight)

• . It contains large numbers of integral proteins called porins. These porin form channels that allow molecules 5000 Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other.

• Larger proteins can enter the mitochondrion if a signal sequence at their N-terminus binds to a large multisubunit protein called translocas of the outer membrane, which then actively moves them across the membrane

Intermembrane space• The intermembran space is the space between the outer

membrane and the inner membrane. It is also called as Perimitochondrial space.

• Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol.

• However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol

• One protein that is localized to the intermembrane space in this way is cytochrome c

The inner mitochondrial membrane contains proteins with five types of functions:• Those that perform the redox reactions of oxidative

phosphorylation• ATP synthase, which generates ATP in the matrix• Specific transport proteins that regulate metabolite passage

into and out of the matrix• Protein import machinery.• Mitochondria fusion and fission protein.

Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1.

*Inner membrane

• The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP.

• For typical liver mitochondria, the area of the inner membrane is about five times as great as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae.

• These folds are studded with small round bodies known as F1 particles or oxysomes. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function.

One recent mathematical modeling study has suggested that the optical properties of the cristae in filamentous mitochondria may affect the generation and propagation of light within the tissue.

*Cristae

• The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion.

• The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane.

• The matrix contains a highly-concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.

• Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes: 22 tRNA, 2 rRNA, and 13 peptide genes.

*Matrix

Function• The most prominent roles of mitochondria are to produce the

energy currency of the cell, ATP (i.e., phosphorylation of ADP), through respiration, and to regulate cellular metabolism.

• The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs Cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

• Regulation of the membrane potential• Apoptosis-programmed cell death• Calcium signaling (including calcium-evoked apoptosis)• Regulation of cellular metabolism• Certain heme synthesis reactions.• Some mitochondrial functions are performed only in

specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism.

* The human nuclear and mitochondrial genomes

Nuclear Genome Mitochondrial Genome

Size 3200 Mb 16.6 kb

No. of different DNA molecules

23 (in XX cells) or 24 (in XY cells); all linear

One circular DNA molecule

Total no. of DNA molecules per cell

46 in diploid cells, but varies according to ploidy

Often several thousands (but variable

Associated protein Several classes of histone & nonhistone protein

Largely free of protein

No. of genes ~ 30 000 ~35-000 37

Gene density ~ 1/100 kb 1/0.45 kb

* Table continued……..

Repetitive DNA Over 50% of genome Very little

Transcription The great bulk of genes are transcribed individually

Co-transcription of multiple genes from both the heavy and light strands

Introns Found in most genes Absent

% of coding DNA ~ 1.5% ~ 93%

Codon usage Slightly different see slide

Recombination At least once for each pair of homologs at meiosis

No evidence for this occurring naturally

Inheritance Mendelian for sequence on X and autosomes; paternal for sequence on Y

Exclusively maternal

Outer membrane

*The membrane is smooth

*Protein content is roughly

equal to that of lipids

.

Enzymes-

* Monoamino oxidase

*NADH cytochrome reductase

*Hexokinase2-Glycerophosphate acyl transferase

Inner membrane

*Membrane bears larger umber of F0-F1 particles

*Protein content is 80%while lipid is low

Enzymes-

*ATPase

*Succinic dehydrogenase

*Cytochrome oidase

*3-Hydroxy butyrate dehydrogenase

*Difference between inner n outer mito membrane

An affected woman transmits the trait to all her children. Affected men (represented by squares do not pass the trait to any of their offspring

Maternal genetic transmission

* Number of Mitochondria per cell

*Most somatic cells 100-10,000

*Lymphocyte 1000

*Oocytes 100,000

*Sperm few hundred

*No mitochondria in red cells and some terminally differentiated skin cells

*Some diseases associated with mitochondrial mutations

MERRF (Myoclonic Epilepsy with Ragged Red Fibres

MELAS (Myopathy,Epilepsy Lactic acidosis,Stroke-like episodes

LHON (Leber’s Hereditary Optic atrophy)

Kearn-Sayre (eye problems,heart block,ataxia ie loss of coordination

Leigh syndrome(rare severe brain disease in infancy,also heart problems)

* mtDNA contribution to the reconstruction of human history

Depends on:-

• High mutation rate (especially in D loop region)

• Maternal transmission

• No recombination

This allows the origins of female ancestors to be deduced

*Conclusion*Many workers believe the mitochondria of eukaryotic cell to have arisen from a prokaryotic cell which invaded another eukaryotic cell in the recent past.this assumption is based on the fact that the mito has a single ringed DNA molecule like that of the prokaryotic cell.

*THANK YOU