A critical player in glucose uptake is the pancreas, whose beta-cells release insulin. This hormone signals for cells to open their gates to glucose, which causes the blood glucose level to decrease. A sudden drop in blood glucose leaves us with that comatose feeling we all associate with the Thanksgiving repast, that leaves us with the irresistible urge to take a nap on an indulgent relative’s couch.
At the heart of these metabolic matters is the mitochondrion, the organelle responsible for all the power conversions in the cell, and the cause – when its function is perturbed – of a wide variety of metabolic diseases. The mitochondrion is a structure unique to eukaryotes, meaning it has no place in the bacterial kingdom. But it’s less than a micron in diameter, making it about the same size as a typical prokaryote.
The mitochondrion is the cell’s generator, providing a power supply in the form of adenosine triphosphate. ATP, as this molecule is known to biochemists, is an important source of chemical energy used by cells to carry out diverse reactions. These processes include completion of cellular signal cascades that allow your brain to process sensory inputs, such as tastes or odors; or the synthesis of any molecule of DNA, RNA or protein.
Mitochondria are the bookends of animal life, witnessing and participating in birth and death. In mammals, mitochondria drive sperm toward egg, enabling the powerful microscopic movements of the sperm flagella that enable the two sex cells to meet.
Mitochondria also play an important role in apoptosis, an organized process by which a cell commits suicide. This might sound morbid and perverse, but programmed cell death is crucial to life – we wouldn’t last very long without it. In worms, for instance, nurse cells die naturally, nurturing the growth of nascent oocytes in the germline.[1]
In our bodies, some tissues must continually regenerate themselves, and this process intimately relates to the death of other, older cells. Whenever an internal cue stimulates cell suicide, you can bet the mitochondrion plays a role, as there are key cell death proteins attached to the outer mitochondrial membrane, awaiting activation.
It seems serendipitous to me that these tiny organelles moving around in my cells are the same size as a bacterium, and have many of the same properties as bacteria. In fact, there is a reason for this. Evolutionary theory posits that mitochondria resulted from the engulfment of eubacteria by larger eukaryotic cells about 2,000 million years ago. That might seem like hostile behavior on the part of the eukaryote, but in fact, it’s worked out rather well for both parties. On the one hand, the host cell – us – takes advantage of the ATP production machinery that the bacterium worked out for itself through evolution. On the other hand, the bacterium has gotten eternal access to the ultimate Toys ‘R Us of chemical substrates, which it can stockpile for its own cellular processes. I guess I don’t mind the thought that there are ancient critters speckled throughout my body, so long as they keep my blood sugar balanced when I’ve eaten one too many slices of pie at Thanksgiving dinner.
As it turns out, the mitochondrion has been crucial to understanding a variety of metabolic diseases, or instances when the body’s ability to break down sugar has been compromised. The earliest mitochondrial disorder was discovered in the late 1950’s and was termed Luft’s disease after Rolf Luft, a Swedish endocrinologist. The study described the health of a 35-year-old woman, who – at 5 feet 2 inches – weighed less than 85 pounds, although she ate more than 3,000 kilocalories per day. The woman also complained of heavy and constant perspiration, and she drank unusual volumes of water. Luft focused his query on her skeletal muscles, where he discovered elevated levels of one of the components of the electron transport chain, critical to ATP production. Under the electron microscope, Luft observed that mitochondria of various sizes and shapes had accumulated in the patient’s muscle tissue, which first alerted him that the condition related to a mitochondrial defect.[2]
Other examples of mitochondrial disease abound: Alzheimer’s disease, Huntington’s disease, and diabetes, to name a few. Because mitochondria work less efficiently over time, we all suffer under the weight of a mitochondrial disorder, which just gets more serious as we age.
The story is even more interesting today than it was in Luft’s time, because of the wealth of information that scientists have since accumulated. One recent study posited that there were an astounding 1,098 mammalian proteins in the mitochondrion, much more than earlier estimates. Many of these proteins are uncharacterized, meaning that they may turn out to underlie metabolic disease in novel ways.[3]
In the future, doctors may perhaps use information about our genetic makeups to diagnose, and even to treat, diseases of the mitochondrion. In the process, humans will live longer lives, and will be able to enjoy more of those Thanksgiving dinners, though perhaps with more of an eye for moderation.
[1]
http://www.wormbook.org/chapters/www_programcelldeath/programcelldeath.html
[2]
http://www.ncbi.nlm.nih.gov:80/pmc/articles/PMC291101/?report=abstract
http://www.ncbi.nlm.nih.gov/pubmed/18614015?ordinalpos=3&itool=EntrezSys...
