Mitochondrial replication is diagrammed in the cartoon. Mitochondria replicate much like bacterial cells. When they get too large, they undergo fission. This involves a furrowing of the inner and then the outer membrane as if someone was pinching the mitochondrion. Then the two daughter mitochondria split. Of course, the mitochondria must first replicate their DNA. This will be discussed in more detail in the next section. An electron micrograph depicting the furrowing process is shown in these figures. The figure on the right was taken from Fawcett, A Textbook of Histology, Chapman and Hall, 12th edition, 1994

 Sometimes new mitochondria are synthesized in centers that are rich in proteins and polyribosomes needed for their synthesis. The electron micrograph in the following figure shows such a center. It appears that the cluster of mitochondria are sitting in a matrix of proteins and other materials needed for their production. How might you prove that material in that region was making mitochondrial proteins?

Mitochondria have their own DNA and Ribosomes

Mitochondria have some of their own DNA, ribosomes, and can make many of their own proteins. The DNA is circular and lies in the matrix.in punctate structures called "nucleoids".  Each nucleoid may contain 4-5 copies of the mitochondrial DNA (mtDNA).

Is it normal to have areas with many mitochondria?  Yes in some cells and situations.  An example would be the hummingbird flight muscle which has many mitochondria and many cristae in the mitochondria. 

What would happen if a mitochondrion could not undergo fission?  It would continue to grow and grow and eventually become a huge organelle.  Mutant yeast can be produced in which mitochondria are unable to divide.\

When is replication not normal?  Below shows replication and production of cristae in response to defective mitochondria and low ATP.  If ATP is low, the cell is stimulated to make more mitochondria.  But, if they are defective as in the  photograph, ATP cannot be produced.  To compensate, mitochondrial will make more cristae (see the mitochondrion on the right.

Mitochondrial DNA and Ribosomes.

To visualize the structure of mitochondrial DNA, we have to extract the DNA and float it on a water surface. Then, it can be picked up by a plastic coated grid, and examined in the electron microscope. Mitochondrial circular DNA is shown in this figure. This electron micrograph is taken from Fawcett, A Textbook of Histology, Chapman and Hall, 12th edition, 1994.

Human mitochondrial DNA is 16,569 bp; encodes a number of mitochondrial proteins

• Subunits 1, 2, and 3 of cytochrome oxidase
• Subunits 6, 8,9 of the Fo ATPase
• Apocytochrome b subunit of CoQH2-Cytochrome C reductase
• Seven NADH-CoQ reductase subunits

Mitochondria also have their own ribosomes and tRNA:

• 22 tRNAs
• rRNAs
  16S, 12S, 5S

Mitochondrial Inheritance

In mammals, 99.99% of mitochondrial DNA (mtDNA) is inherited from the mother.  This is because the sperm carries its mitochondria around a portion of its tail and has only about 100 mitochondria compared to 100,000 in the oocyte. As the cells develop, more and more of the mtDNA from males is diluted out.  Hence less than one part in 10⁴ or 0.01% of the mtDNA is paternal.  This means that mutations of mtDNA can be passed from mother to child.  It also has implications if one does cloning of mammals with the use of  somatic cells.  The nuclear DNA would be from the donor cell, but the mtDNA would be from the host cell.  This is how Dolly the sheep was cloned.  The following diagram shows a family in which the mother passed the mutation to her three children, but only the daughters passed it to subsequent generations.

Mutations in mammalian mtDNA do cause diseases, because there is such a short sequence and very heavy information content in the sequence.  Since each cell contains hundreds of mitochondria and thousands of copies of the genome, the effects of the mutated mitochondria may be diluted out.  As expected, those tissues or organs most likely to be affected would be the ones most dependent on oxidative phosphorylation (ATP production). In young persons it might not be picked up because even a person with 15% normal mitochondria might have enough to be healthy.  However, aging patients may show a more severe disease phenotype.    Also, the mother passes the mutation unevenly to the different daughter egg cells.  See the following figure.  This uneven distribution may result in some children with lethal forms of the disease and others with mild forms.

Some example of diseases: 

• Leber's hereditary optic neuropathy (degeneration of the optic nerve, accompanied by increasing blindness): caused by mutation to the gene encoding subunit 4 of the NADH-C0Q reductase.   
• "ragged muscle fibers" associated with jerky movements is caused by mutation of mitochondrial lysine tRNA.
• Kaerns-Sayre syndrome: eye defects, abnormal heartbeat, Central nervous system degeneration.  Several large deletions in mtDNA.  
• types of Type I diabetes
•  

Some mutations involve a simple change in a base.  Changes may have varying effects, however, as shown in the figure to the left. .  This is Mitochondrial tRNA for leucine. A mutation in this tRNA would never be cured by  tRNA encoded by the nucleus.

This figure shows variability in the disease with substitutions in bases in one of the mttRNAs. Note the number of diseases

This figure shows that mammalian mrDNA has a unique genetic code. This makes it traceable and one can trace one's ancestors via maternal lines.  This also helps to identify victims and is thus used in forensic medicine.

What happens to old, worn-out mitochondria?

Mitochondrial numbers are controlled by autophagy. This is a process by which lysosomes are involved in controlling cell constituents. This Figure shows the process; it is taken from Fawcett, A Textbook of Histology, Chapman and Hall, 12th edition, 1994.

The process begins by wrapping endoplasmic reticulum membranes around the mitochondrion. Then, vesicles come from the Golgi complex and join with the autophagic vacuole. These vesicles contain hydrolases attached to the mannose 6 phosphate receptors in the vesicle membranes. The lysosome web page discusses their function and fate. Recall that they fuse with the autophagic vacuole.   The acid pH then allows the hydrolases to be removed from their receptors. The receptors are recycled back to the Golgi complex in other vesicles.