TransTech Digest: Why Mitochondria Matter

I may sound like a broken record saying this again, but it’s critical that we realize that scientific understanding of the biological world is increasing at an exponential rate. For younger readers, I should explain that the term “broken record” is a reference to a common failure of the old pressed-vinyl audio recording technology. Occasionally, the spiraled groove on a record imprinted with physical representations of sound would be scratched or otherwise damaged. As a result, the needle that transferred analog information to the amplifier would be knocked outward from the groove to play the same section of the recording over and over again. For those of you who already knew this, it’s useful to realize that the technology of audio recording that was once universal is not just obsolete, most younger people don’t even know what a skipping record is today. The reason that this is such a useful realization is that biotechnology has undergone even bigger changes than the transformation of recorded music from bumps in vinyl grooves to streamed electrons. Most people, however, have no real appreciation of how big the ongoing biotech transformation really is. New tools let us see deep into the atomically precise world of molecular biology. Just as important is a growing base of biological knowledge that is available to anybody. Though Google Scholaris only 10 years old, I find it hard to imagine a world without instant access to peer-reviewed literature. GeneCards, which is only 15 years old, puts the combined body of genomic knowledge at your fingertips and has recently added cell development and disease pathogens as well as analytical tools to its master databank. Among the most exciting areas of modern biological research is mitochondria and the role of a molecule critical for their function, nicotinamide adenine dinucleotide (NAD). In terms of scientific research, our growing understanding of these tiny bacteria-like mitochondria inside every cell of the body is breaking news. Weekly, we seem to be learning something critical about the relevance of metabolic efficiency, on the biochemical level, to long-term health. Only recently have we learned that mitochondria play a much larger role in the diseases of aging than previously known. This means research into the mechanisms of mitochondria and their interactions with the rest of the cell may lead directly to extended health spans. This is why I think that you should be interested in this subject. As scientific knowledge grows, and the popular media is increasingly overwhelmed by this explosion of data, individuals will need to keep abreast of science to take advantage of new possibilities. This may not have been necessary in the days of vinyl record, but those days are gone. A few years ago, we saw a number of papers like this one. The authors, in 2009, proposed that protection of mitochondrial function would result in increased longevity. The article describes how mitochondrial function in muscle cells declines over time, suggesting that it may be related to oxygen uptake. This leads the authors to recommend long-term aerobic exercise as a solution. While I believe that exercise, though not solely aerobic exercise, is an important part of health maintenance, more recent research suggests that there are other effective ways to prevent the decline of mitochondrial health. Before I get into the intricacies of just how mitochondrial function can be affected positively, we should go over background information on what a mitochondrion is and how, in layman’s terms, it harvests energy from sugar molecules to power cellular processes.

The Mitochondrial Basics

The discovery of mitochondria occurred over the second half of the 19^th century as the improvement of microscopes and associated technologies provided insights into the world of cells. In 1894, the scientist who developed new ways to preserve cells for microscopic analysis, Richard Altmann, coined the term “bioplasts” to describe mitochondria. What these cells within cells actually did, however, was not clear. Given the size of a mitochondrion and the primitive tools available for studying them, this was not surprising. Mitochondria measure one micrometer across. That’s one thousandth of a millimeter or a micron. To put that in perspective, the size of a human red blood cell is usually about five microns. In textbooks and in many diagrams on the Internet you will see one or two mitochondria in the cell. In fact, there may be thousands of them, all converting stored energy in the chemical bonds of our food into usable energy currency called ATP, which is short for adenosine triphosphate. ATP is comprised of an adenosine molecule with three phosphate groups bonded in a chain to it. Inside the outer membrane of the mitochondrion resides yet another layer of membrane, which folds up into itself many times. This layered membrane is referred to as the matrix, and it contains within it enzymes that work to further break down glucose molecules. In most biology 101 classes you will get a review of all the “organelles” of a typical human-like cell. One of the most important is the mitochondria, which function as the power supply to the rest of the cell. The average human contains only about half a pound of total ATP in their body, but the astounding fact is how much that ATP turns over. In just one day, the average human goes through about 60 septillion molecules of ATP. This equates to our own body weight in ATP being processed and recycled each day.

Mitochondria, the Aliens Within

Mitochondria are fascinating not only because they are so vital to virtually every biological process, but also they are distinct from all other organelles of a cell. Two peculiar things about the mitochondria’s structure stand out. First, there’s the matter of packaging. Every large organelle, including the nucleus that protects the DNA, is contained with a membrane. This is the same kind of membrane that surrounds, and encapsulates, the entirety of the cell. Mitochondria are the only exception. Mitochondria, for some reason, have two membrane layers surrounding them, just like bacteria. Secondly, mitochondria are the only organelles that contain DNA besides the nucleus. Whereas the DNA of your genome is linear (with a beginning and an end), mitochondrial DNA is circular, just like bacterial DNA. The similarity of mitochondria to bacteria is extremely important. Bacteria are independent organisms, but they can cooperate in quite astonishing ways by transferring chemically coded information among themselves. This ability helps them, for example, pass immunities to antibiotics to others of their species. Scientists have actually harnessed this ability to build a type ofbacterial computer capable of solving complex problems. This is not simply some bit of interesting trivia. Perhaps the central realization in the new science of mitochondria is that our mitochondria function like a biological computer network. Singly, a mitochondria has 37 genes, compared to the tens of thousands of protein-coding genes in the DNA of the nucleus. Mitochondria, however, often have multiple copies of their circular DNA plasmids, and there can be thousands of mitochondria in a cell. Mitochondria, like bacteria, split and merge and repeat the process with other mitochondria innumerable times. Unlike bacteria, however, they operate in conjunction with the master genome in the cell’s nucleus. We are only beginning to understand everything that mitochondria do, but only a few percent of the mitochondrial DNA is involved with the critical production of ATP. This leaves a lot of computation capacity for other functions. So we are beginning to see this mitochondrial network in a new and far more important light. More importantly, we’re beginning to understand how this network fails as we age and how this failure impacts many areas of health. We’ll get to this later, but I will say here that there are ways to rescue this network even when we are quite old. To understand how we can do this, we should understand at least the basics of mitochondrial energy function.

Cellular Respiration: Three Not-So-Simple Steps

Mitochondria are found in human cells, mammal cells, animal cells, and plant cells. In fact, the presence of mitochondria is one of the characteristics that biologists use to distinguish eukaryotic cells (these are the cells that make up all animals, plants, and fungi) taxonomically from prokaryotic cells like bacteria. There are a few other distinctions, the most important being the presence of a nucleus in our cells (eukaryotic cells). As you know, the nucleus contains and protects our entire genome like a vault or an encrypted hard drive. Mitochondria are the power grid for the entire cell including the nucleus, which uses the energy for numerous and complex molecular biological processes that go on within. They take in molecules of glucose through the several metabolic pathways, harvest the energy, and store it as ATP for intercellular use. The first step in converting glucose into energy is called glycolysis, which actually doesn’t happen in the mitochondria but in the cytosol of the cell (the cytosol is the liquid that fills up our cells). Glycolysis basically works like a pair of scissors, cutting glucose molecules precisely in half from six carbons long to only three. These chopped up glucose molecules are now called pyruvate, and these are the molecules that actually enter into the mitochondria’s matrix. Once inside the mitochondrion, the pyruvate goes through the citric acid cycle, a set of biochemical reactions far too complex for me to even begin to explain here. Instead I’ll just tell you what the results are. We do get a little bit of ATP from the citric acid cycle, but not nearly as much as in the electron transport chain. The most important part of the citric acid cycle is the transfer of hydrogen atoms from the pyruvate to NAD+ and FAD+, which then turn into their reduced forms NADH and FADH_2, respectively. In chemical terms, reduction/oxidation reaction is defined as the transfer of electrons to or away from a molecule. In many biological functions, however, the transfer of entire hydrogen atoms is also considered reduction or oxidation. So when a hydrogen is transferred from a pyruvate derivative, it’s considered to be reduced. And when that hydrogen atom bonds to an NAD+ molecule, it’s considered to be reduced. After they receive the hydrogen atoms, they become NADH and FADH₂. NADH and FADH₂ then head into the electron transport chain, which you might guess concerns itself mostly with the transfer, or transport, of electrons. Again, without getting too far into the nitty-gritty biochemical details, the electron transport chain works essentially like a water mill. The water mill harnesses the energy of water flowing toward a lower state of potential energy. The water, which starts at both a higher elevation and a higher energy state, performs work on its way to water’s ultimate resting place: ocean level. The electron transport chain works exactly the same way but with the flow of electrons instead of water. Electrons, because they are negatively charged, want to “flow” toward the nuclei of the atoms they surround because nuclei are made of positively charged protons. You can think of electrons as screaming fans, the nuclei as the Beatles in the mid-1960s, and the electron transport chain as the box office. The electron transport chain lets them get closer to the positive charges, but before it does, it must stamp their tickets and receive payment in the form of energy. Today I have attempted to give a very broad overview of the processes involved in cellular respiration, the main function of a mitochondrion. I want this information to be the backdrop for the new and exciting story of repair, which I intend to tell you about in next week’s editorial. Sincerely, Patrick Cox To learn more about the new research driving Patrick’s investigations at his Transformational Technology Alert letter for Mauldin Economics, click here.