This video is a nice illustration of the incredible advances of molecular biology in the past 25 years. When I was a medical student, a long time ago, we learned all the anatomic structures of the cell but had no idea what many of them did. We knew that mitochondria made energy from oxygen but, aside from basic genetics (very basic) we didn’t understand most of what went on in the cell. Over the past six or seven years, I have spent some time reading about molecular biology so I could appreciate what has been learned and in an attempt to appear better informed to my students. Along the way, I got very interested in mitochondria.
First, a nonbiologist must learn the difference between a Eukaryote and a Prokaryote. A eukaryote is a cell, or an organism made up of cells, that has a nucleus (containing the chromosomes) enclosed by a membrane and a structure of cell organelles that carry out cell functions. Plants, for example, are eukaryotes and have a larger number of genes than humans do. They also have mitochondria. The prokaryote has its genetic material, often a single chromosome, lying free in the cytoplasm. Bacteria are prokaryotes. Yeasts are eukaryotes with nuclei.
If you don’t believe in evolution, it would be best if you stopped reading here.
It is generally accepted that the first living cells were some form of prokaryote and may have developed out of protobionts. Fossilized prokaryotes approximately 3.5 billion years old have been discovered (less than 1 billion years after the formation of the earth’s crust), and prokaryotes are perhaps the most successful and abundant organism even today. Eukaryotes only formed later, from symbiosis of multiple prokaryote ancestors; their first evidence in the fossil record appears approximately 1.7 billion years ago, although genetic evidence suggests they could have formed as early as 3 billion years ago.
Protobionts are thought to be the precursors of living cells. Maybe the prion, which causes mad cow disease is actually the ancestor of all life. Because of the extreme conditions existing early in the Earth’s history, proteins may have been the original genetic material. Christian de Duve, a Nobel Prize winning biologist, has written a book on the subject. Until the discovery of DNA, proteins were thought to be the genetic material by most biologists. Frederick Griffith began the modern field of genetics when he discovered Transforming Material, which was DNA. DNA “melts” at 87 degrees centigrade, however, and RNA, which will tolerate higher temperature, does not seem to be able to replicate itself without DNA. The origins of life may involve self replicating proteins, like prions.
There has been considerable interest in Archea, a class of organisms found in extreme conditions, because they may have been able to survive in those conditions. Perhaps, they were the first life forms. Originally thought to be bacteria, and first called “Archaeabacteria”, they are quite different and have a different cell membrane composition. First discovered in extreme conditions, like steam vents in the ocean floor or geysers, they are now recognized as widely distributed in all conditions, including ocean plankton. Craig Venter, whom I have previously discussed is collecting ocean water samples looking for useful Archaea samples to study their genome. They may hold the solution to the energy problem, for example.
Mitochondria were probably early prokaryotes in the evolution of life. They carried a unique characteristic. They can create energy from oxygen. As the earth cooled and plants began to develop, the atmosphere, at first made up of methane (which Archaea love) and carbon dioxide (which plants use as fuel), began to contain measurable oxygen. The ability to use that oxygen became desirable. The origin of mitochondria has stimulated intense research. Mitochondria may have been ingested by early eukaryotes and, because they carried the ability to use oxygen and produce more energy than anerobic metabolism, the relationship may have changed from predator to cooperation. Genome sequencing has allowed proof of theories that were only speculation 25 years ago. The mitochondrion has its own DNA. It was almost certainly once freeliving but, as it adapted to symbiosis, it lost unused genes until some types have only three. The study of mitochondrial DNA has contributed to the study of human origins. The “African Eve” theory is derived from the fact that all mitochondria are inherited from the mother. There are no mitochondria in the sperm.
UPDATE: An astute reader pointed out that my statement above is incorrect. Actually, it is a sign of how old I am as this was the previous understanding. However, sperm do have mitochondria but they are tagged for destruction and do not survive in the egg. Why this is, is not explained although the paternal mitochondria may be harmful in some fashion.
Other evidence that mitochondria were once free living come from the study of Rickettsia, cause of diseases such as typhus (which defeated Napoleon’s Grand Army in Russia) and Rocky Mountain Spotted Fever. The organism is named for Ricketts who discovered the organism and lost his life in the process.
That’s enough cell biology for a Saturday morning. The basics of evolution are contained in this story, however.
Tags: Archaea, cell biology, eukaryote, evolution, mitochondria, prokaryote, Rickettesia
Wow, that’s fascinating, Mike. I don’t trust anaerobic bacteria, because that is what causes tooth decay – and it’s very hard to get rid of bacteria that doesn’t need oxygen. I think if oxygen does reach it, then it can die- if I remember my dentist correctly. He’s in Beverly Hills and insists that we look at his drawings and explanations of how things work. The stars must love it.
I wonder what position the mitochondria would have today, positive or negative, if they had gained the position of power bacteria have.
Bacteria don’t have mitochondria so they are probably responsible for multi-celled organisms like us. There is low level aerobic metabolism without mitochondria but it isn’t very efficient. Rinse your mouth with weak peroxide. That gets those little devils.
A fun article, Dr. K.
Energy metabolism is interesting. It is all about getting high energy electrons from food. As we break down our food, we generate NADH (which carries those high energy electrons). Then our mitochondria look for the lowest energy acceptor possible. That’s oxygen. The difference in potential between NADH and oxygen gets captured in the form of ATP, the energy currency of the cell.
So, the electrons come from our food, and they are “dumped” onto oxygen (which generates water). The question for students is thus: why do we need to breathe oxygen? Answer: to have a place to dump those electrons!
I have students hold their breaths, and raise their hands when they feel discomfort. When they do, I tell them that they have too many electrons!
Peter Mitchell, who discovered much of this, is an interesting person about whom to read.
http://en.wikipedia.org/wiki/Peter_D._Mitchell
http://www-biology.ucsd.edu/~msaier/transport/petermitchell/MitchellFrame-1.html
http://www.life.uiuc.edu/crofts/bioph354/mitchell.html
Best wishes….
Hope this is just a teaser of more to come…I’m lovin’ it.
Fascinating.
“The “African Eve” theory is derived from the fact that all mitochondria are inherited from the mother.”
Way in the background I think I heard this on a talk show: someone suggested Mexico should annex the American Southwest, since at one time they owned it. Someone else called in and thought the American Indians should annex Mexico, since at one time they owned it. Then someone called in and said a lady in Tanzania once owned the whole world, so we owe everything to Africa.
That was fascinating. I didn’t understand half of it, but the parts I did were made soooo much clearer. Someone put some serious sweat into that animation.
But…you say “There are no mitochondria in the sperm.”?
I thought there are, but that they are destroyed (absorbed and disassembled really) by the egg, along with all the rest of the sperm hardware – except the DNA core – after fertilization?
Not criticizing – just trying to confirm a correction on my (assumed) knowledge.
I left out “Since the sperm mitochondria are physically destroyed, they cannot be inherited by the newly forming child.”
Mr. McGoo: what you wrote is true. I cannot see how sperm motility—based on ATP and dynein and microtubules—could avoid mitochondria.
Thanks, Eric. Since the point is firmly peripheral to the most-excellent discussion presented, I assume Dr. K perhaps took a dab of literary license to avoid an unnecessary side trip.
Outstanding stuff, Dr. K. As I said – its fascinating.
I stand corrected. The point about motility should have made me look at that again.
As others have said, Dr. K: no big deal. We are grateful that you posted the article. Fun stuff, and thought provoking.
I’m trying to find the name of the European MD or PhD who was trying to think of a new subject for his research while lying on the beach. This was in the late 50s or 60s. He started thinking about mitochondria and that began the work on the relationship with Rickettsia. I have it somewhere.
On the Beach. I saw the movie.
I was lying on the beach when my two roommates convinced me to switch to pre-med. Lots of good things happen lying on the beach but that movie scared me too much. I haven’t watched it, or read the book, in years.
Regarding mitochondria, sperm, and uniparental inheritance, I thought that you might be interested in the following, Dr. K. It turns out that the paternal mitochondria get ubiquinated—marked for destruction—and that appears to be the basis for the uniparental inheritance.
Check out this abstract:
Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G. (2000). “Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos..” Biol Reprod. 63(2):582-90.
Abstract:
The strictly maternal inheritance of mitochondria and mitochondrial DNA (mtDNA) in mammals is a developmental paradox promoted by an unknown mechanism responsible for the destruction of the sperm mitochondria shortly after fertilization. We have recently reported that the sperm mitochondria are ubiquitinated inside the oocyte cytoplasm and later subjected to proteolysis during preimplantation development (P. Sutovsky et al., Nature 1999; 402:371-372). Here, we provide further evidence for this process by showing that the proteolytic destruction of bull sperm mitochondria inside cow egg cytoplasm depends upon the activity of the universal proteolytic marker, ubiquitin, and the lysosomal apparatus of the egg. Binding of ubiquitin to sperm mitochondria was visualized by monospecific antibodies throughout pronuclear development and during the first embryonic divisions. The recognition and disposal of the ubiquitinated sperm mitochondria was prevented by the microinjection of anti-ubiquitin antibodies and by the treatment of the fertilized zygotes with lysosomotropic agent ammonium chloride. The postfecundal ubiquitination of sperm mitochondria and their destruction was not seen in the hybrid embryos created using cow eggs and sperm of wild cattle, gaur, thus supporting the hypothesis that sperm mitochondrion destruction is species specific. The initial ligation of ubiquitin molecules to sperm mitochondrial membrane proteins, one of which could be prohibitin, occurs during spermatogenesis. Even though the ubiquitin cross-reactivity was transiently lost from the sperm mitochondria during epididymal passage, likely as a result of disulfide bond cross-linking, it was restored and amplified after fertilization. Ubiquitination therefore may represent a mechanism for the elimination of paternal mitochondria during fertilization. Our data have important implications for anthropology, treatment of mitochondrial disorders, and for the new methods of assisted procreation, such as cloning, oocyte cytoplasm donation, and intracytoplasmic sperm injection.
That’s the article referred to by the link I posted in my Update. I’m chugging away at Lewin who points out the bad effects of loss of telomeres. Maybe it is a similar thing. Cell death may be good for the species. I have a long way to go but will post updates as I do so. The next will probably be about embryology and evolution.
Eric, that abstract gives me the shivers.
Donna B., scientists love their jargon. Why use a two syllable word when a five syllable word will do? Actually, most of the things scientists discover are pretty straightforward. Ubiquitin is a protein “tag” that tells the cell’s machinery to trash whatever item has that tag. Ah, but what controls where and when those tags are added to molecules? That’s the Nobel Prize question!
But it is interesting to note that ubiquitin tags get added to the spermatozoal pronuclei. Cool.
I share your interest in telomeres, Dr. K. Here is a great book to read, about the Rise and Fall of the biotech company Geron:
“Merchants of Immortality: Chasing the Dream of Human Life Extension ,” by Stephen H. Hall. 2005.
Quick background on Geron:
http://en.wikipedia.org/wiki/Geron_Corp.
Two types of cells express telomerase: cancer cells and the gametogenic cells that make sperm and eggs. What started as a quest to let us live forever is now a target for cancer therapy.