{"id":321,"date":"2020-08-07T12:00:00","date_gmt":"2020-08-07T16:00:00","guid":{"rendered":"https:\/\/anyonecanscience.com\/?p=321"},"modified":"2020-08-06T19:48:25","modified_gmt":"2020-08-06T23:48:25","slug":"disorders-of-mitochondrial-dna","status":"publish","type":"post","link":"https:\/\/anyonecanscience.com\/index.php\/2020\/08\/07\/disorders-of-mitochondrial-dna\/","title":{"rendered":"The Genetic Blueprint of Disease: Part 5\u2014Disorders of Mitochondrial DNA"},"content":{"rendered":"\n

These past few weeks, I have written about many different genetic disorders<\/a> and risk factors<\/a> that stem from inherited errors<\/a> in the DNA or mistakes in the division of chromosomes<\/a>. But this week, I want to pivot a bit to talk about disorders that originate in a special form of DNA called mitochondrial DNA (mt<\/a>DNA). Most of the DNA in your cells is housed within the nucleus, a central organelle (literally \u201clittle organ\u201d\u2014organelles are the \u201corgans\u201d of your cell with their own specific function). The nucleus keeps the DNA separate from all of the enzymes and chemical reactions of the cell. DNA spends most of its life inside the nucleus until the nucleus breaks down at the start of mitosis or meiosis. But nuclear DNA isn\u2019t the only type of DNA in the cell. Another group of organelles called the mitochondria contain their own set of DNA, the mtDNA, that is unique and separate from the nuclear DNA. <\/p>\n\n\n\n

Mitochondria are the only organelles in human or animal cells that have their own DNA. Scientists believe that this is because mitochondria used to be independent cells that were \u201cswallowed\u201d by bigger cells. The ancient mitochondria formed a symbiotic relationship with the cell and evolved into the mitochondria we have today. Mitochondria are responsible for converting oxygen to energy that the cell can use (you may have heard the phrase \u201cmitochondria are the powerhouse of the cell\u201d<\/a>). As such, disorders of the mitochondrial DNA often have disastrous consequences for cellular functioning.<\/p>\n\n\n\n

In a literal sense, a \u201cpowerhouse\u201d is a place where electricity is created, usually by burning fuel and converting the heat energy that is released into kinetic and then electrical energy<\/a>. This process takes advantage of the chemistry of hydrocarbon combustion<\/a>. Combustion requires a hydrocarbon fuel (like coal, petroleum, methane, alcohol, etc.), a supply of oxygen (this is why you can \u201csuffocate\u201d a fire or suffocate in a fire), and an initial source of heat (the spark). The energy stored in the chemical bonds of the hydrocarbon is released during combustion as heat and the carbons, hydrogens, and oxygens recombine to create byproducts of carbon dioxide (CO2) and water (H2O). Combustion is a highly exothermic reaction, meaning it produces more energy than it takes in. Depending on the fuel, combustion can produce large amounts of heat energy that can be converted into kinetic or electrical energy.<\/p>\n\n\n\n

\"Coal
Photo by\u00a0Michal Matlon<\/a>\u00a0on\u00a0Unsplash<\/a>
Coal combustion is a common source of energy<\/figcaption><\/figure><\/div>\n\n\n\n

The process that mitochondria, the powerhouses of the cell, use to create energy\u2014called cellular respiration\u2014is actually much more complicated than the combustion and energy conversion that occurs in a real powerhouse. The full process of cellular respiration<\/a> is a mess of chemical reaction cycles, protein pumps, and potential energy gradients (trust me\u2014you never want to learn the Krebs cycle unless you have to). But, in terms of what it requires and what it creates, cellular respiration is actually quite similar to the combustion used in real powerhouses.<\/p>\n\n\n\n

The first thing required for cellular respiration is a hydrocarbon fuel, in this case glucose. Glucose is harvested from food or fat stores in the body and distributed to cells through the bloodstream. Glucose can be processed into small amounts of energy without oxygen through a process called glycolysis<\/a>. When there is no oxygen to continue cellular respiration, a process called fermentation<\/a> occurs instead to regenerate the molecules needed to continue breaking down glucose. Yeast cells use glycolysis and fermentation to create their energy, which has the fortunate (for us) byproduct of alcohol. For humans, fermentation occurs often in the muscles during strenuous exercise (perhaps you just went for a run and as horrendously out of shape as you are, you simply cannot get enough oxygen in your lungs for your poor overworked muscle cells). Instead of alcohol, this form of fermentation creates the (much less fun) byproduct of lactic acid, which is responsible for the soreness you feel for days after a workout.<\/p>\n\n\n\n

\""Cells
“Cells with nuclei in blue, energy factories in green and the actin cytoskeleton in red”<\/a>\u00a0by\u00a0National Institutes of Health (NIH)<\/a>\u00a0is licensed under\u00a0CC PDM 1.0<\/a><\/figcaption><\/figure><\/div>\n\n\n\n

Glycolysis is all well and good, and it occurs independently of the mitochondria, but it doesn\u2019t produce nearly enough chemical energy for a bustling and overworked human cell. The rest of the cellular respiration process occurs within the mitochondria and it requires that staple of combustion, oxygen. Cells are provided with a constant stream of oxygen transported from the lungs by the red blood cells. A break in this supply for too long can be catastrophic, leading to brain damage, organ failure, and eventually death (here\u2019s your daily reminder to breathe<\/em>).<\/p>\n\n\n\n

Just like combustion, cellular respiration utilizes a hydrocarbon fuel (glucose), oxygen, and a small amount of chemical energy (required for glycolysis) to create carbon dioxide, water, and a large net yield of chemical energy. But what do I mean by chemical energy? Cells don\u2019t have electrical grids like cities do, so what does energy actually mean in cellular terms? Turns out, cells store all their energy in a spring-loaded molecule called Adenosine Triphosphate (ATP). ATP is made of adenine (the base found in DNA) with a line of three phosphates (PO3) attached to it. The phosphorous-oxygen bond is so spring-loaded and full of potential energy that breaking the bond (removing one phosphate group) releases a good deal of energy that can do work in the cell. <\/p>\n\n\n\n

Many chemical reactions in the cell aren\u2019t spontaneous (they require more energy than they produce), but the cell is able to make these reactions happen by coupling them with the breakdown of ATP that makes up for the energy deficit. Once ATP is broken down into its inactive form, it has to be \u201crecharged\u201d through cellular respiration. Just as breaking a phosphate off of ATP creates energy, adding a phosphate back to ATP requires energy harvested from the breakdown of glucose. Glycolysis can only generate a net yield of 2 ATP molecules for every molecule of glucose. But with cellular respiration through the mitochondria, cells can produce up to 32 ATP molecules with a single molecule of glucose. For some simpler cells, glycolysis is enough to keep them going, but the incorporation of mitochondria into cells is one of the key events that made more complex life possible. <\/p>\n\n\n\n

\n