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That old powerhouse!

S. Ashraf Ahmed
THE deaths of two former teachers made me contemplate how long should I live! Both of them had lived powerful, healthy, and successful lives. Yet a few years before deaths well into their eighties, they had no senses whatsoever, and were totally dependent on others just to keep on breathing! I sure do not want to face a similar fate.
So I looked for information on Ichcha Mrityu or death by desire - a psychologically controlled, biologically programmed death without invoking the wrath of suicide! What I stumbled into was unexpected.
Mitochondria, a tiny substructure, a thousand to two of which inhabit a single cell in my body, along with others continuously send signals for "killing" billions of cells everyday' that are defective or are no more needed. The process is called "programmed cell death" or "apoptosis" that in the fetal stage also gives rise to separated fingers in our hand, and most likely to the three dimensional shape of each animal.
1 knew mitochondria pretty well because I made its three dimensional cross-sectional model, in the Dhaka University Science Fair in 1973, and had won the top prize. It was dubbed "The Biological Power House" because it produces the universal biological currency or energy, ATP. The power of ATP is generated by oxidation of foodstuffs.
My model consisted of glycolysis - breakdown of glucose into a small molecule, acetyl GoA, occurring outside the mitochondria. Once inside, this small molecule enters a series of reactions called the Krebs or TGA cycle producing carbon dioxide. Here the derived electrons combine with oxygen to form water while making ATP. These steps are mediated through an electron transport chain (ETC) and oxidative phosphorylation (OP) as parts of our respiration.
On a hard board, I showed all the reactions of glycolysis, ETG and OP by ~40 colored tiny bulbs shining on and off as imaginary' electrons flew from one molecule to the next.
I knew that cyanide was a poison because it reacted with cytochrome G oxidase, an enzyme in ETG. What I found new is that because the oxidase cannot form water from oxygen due to cyanide poisoning, the electrons produce radicals and reactive oxygen species (ROS) that damage proteins and lipids of the mitochondria: it can no longer make ATP. Without ATP the cell cannot survive and must be "killed" by apoptosis.
A further dig into the subject revealed that mitochondria are primitive bacteria that were engulfed by a larger cell at the early stage of evolution. Gradually the weak
bacteria surrendered most of its genes to the more powerful chromosomes in the nucleus of the cell. So today, making of 1500 plus proteins that constitute mitochondria must be dictated from the nucleus but only 13 from the inherent circular DNA of mitochondria.
We inherit mitochondria only from mothers. This knowledge led scientists in tracing our ancestry to a common Eve mother in Africa, 50 to 500,000 years ago.
Gompared to the only role of generating ATP in the Biological Powerhouse that I knew as a DU student, today it is firmly established that a large number of diseases are also associated with defects in the mitochondria. These Mitochondrial Diseases include juvenile catastrophic epilepsy, congenital heart defect, visual neuropathy, encelopathy of infants, cardiomyopathies, cerebral white matter disease, ovarian dysfunction, hearing loss, cancer and obesity.
What was interesting is that many of the components of theTCA cycle, OP and ETS included in my mitochondria model four decades ago are now known to be involved in some or all of the diseases mentioned above. A defect, lack, too much or too little presence of them can cause the diseases affecting any organ system, at any age, be inherited maternally or from both parents. Unfortunately no treatment, except lessening of the sufferings, is currently available for any of the mitochondrial diseases.
Studies have indicated that the process of "aging", during which I guess my teachers were lying unconscious, is associated with decreased ETS and OP activities with increased levels of ROS, and apoptotic activity. In apoptosis cytochrome c is released by the mitochondria into cytosol, a feature found in "aging" animals. A death occurring from "aging" must be brought about by a cascade of reactions, to some extent in the mitochondria - my old "Biological Powerhouse"!
The concept of Ichcha Mrityu is documented in the Mahabharat. I look forward to a modern, cognitive-control of my apoptotic events right before my looming vegetative age!
The author, a former Dhaka University teacher, is working as a biomedical scientist in the USA.