Lesson 2: Mitochrondia



Mitochondria are often referred to as the powerhouses of the cell. They help turn the energy we take from food into energy that the cell can use. But, there is more to mitochondria than energy production. Present in nearly all types of human cell, mitochondria are vital to our survival. They generate the majority of our adenosine triphosphate (ATP), the energy currency of the cell. Mitochondria are also involved in other tasks, such as signaling between cells and cell death, otherwise known as apoptosis.

The structure of mitochondria

Mitochondria are small, often between 0.75 and 3 micrometers and are not visible under the microscope unless they are stained. Unlike other organelles (miniature organs within the cell), they have two membranes, an outer one and an inner one. Each membrane has different functions. Mitochondria are split into different compartments or regions, each of which carries out distinct roles.

Some of the major regions include the:

Outer membrane: Small molecules can pass freely through the outer membrane. This outer portion includes proteins called porins, which form channels that allow proteins to cross. The outer membrane also hosts a number of enzymes with a wide variety of functions.

Intermembrane space: This is the area between the inner and outer membranes.

Inner membrane: This membrane holds proteins that have several roles. Because there are no porins in the inner membrane, it is impermeable to most molecules. Molecules can only cross the inner membrane in special membrane transporters. The inner membrane is where most ATP is created.

Cristae: These are the folds of the inner membrane. They increase the surface area of the membrane, therefore increasing the space available for chemical reactions.

Matrix: This is the space within the inner membrane. Containing hundreds of enzymes, it is important in the production of ATP. Mitochondrial DNA is housed here (see below).

Different cell types have different numbers of mitochondria. For instance, mature red blood cells have none at all, whereas liver cells can have more than 2,000. Cells with a high demand for energy tend to have greater numbers of mitochondria. Around 40 percent of the cytoplasm in heart muscle cells is taken up by mitochondria. Although mitochondria are often drawn as oval-shaped organelles, they are constantly dividing (fission) and bonding together (fusion). So, in reality, these organelles are linked together in ever-changing networks. Also, in sperm cells, the mitochondria are spiraled in the midpiece and provide energy for tail motion.

Mitochondrial DNA

Although most of our DNA is kept in the nucleus of each cell, mitochondria have their own set of DNA. Interestingly, mitochondrial DNA (mtDNA) is more similar to bacterial DNA. The mtDNA holds the instructions for a number of proteins and other cellular support equipment across 37 genes. The human genome stored in the nuclei of our cells contains around 3.3 billion base pairs, whereas mtDNA consists of less than 17,000. During reproduction, half of a child’s DNA comes from their father and half from their mother. However, the child always receives their mtDNA from their mother. Because of this, mtDNA has proven very useful for tracing genetic lines. For instance, mtDNA analyses have concluded that humans may have originated in Africa relatively recently, around 200,000 years ago, descended from a common ancestor, known as mitochondrial Eve.

What do mitochondria do?

Mitochondria are important in a number of processes. Although the best-known role of mitochondria is energy production, they carry out other important tasks as well. In fact, only about 3 percent of the genes needed to make a mitochondrion go into its energy production equipment. The vast majority are involved in other jobs that are specific to the cell type where they are found. Below, we cover a few of the roles of the mitochondria:

Producing energy

ATP, a complex organic chemical found in all forms of life, is often referred to as the molecular unit of currency because it powers metabolic processes. Most ATP is produced in mitochondria through a series of reactions, known as the citric acid cycle or the Krebs cycle. Energy production mostly takes place on the folds or cristae of the inner membrane. Mitochondria convert chemical energy from the food we eat into an energy form that the cell can use. This process is called oxidative phosphorylation. The Krebs cycle produces a chemical called NADH. NADH is used by enzymes embedded in the cristae to produce ATP. In molecules of ATP, energy is stored in the form of chemical bonds. When these chemical bonds are broken, the energy can be used.

Cell death

Cell death, also called apoptosis, is an essential part of life. As cells become old or broken, they are cleared away and destroyed. Mitochondria help decide which cells are destroyed. Mitochondria release cytochrome C, which activates caspase, one of the chief enzymes involved in destroying cells during apoptosis. Because certain diseases, such as cancer, involve a breakdown in normal apoptosis, mitochondria are thought to play a role in the disease.

Storing calcium

Calcium is vital for a number of cellular processes. For instance, releasing calcium back into a cell can initiate the release of a neurotransmitter from a nerve cell or hormones from endocrine cells. Calcium is also necessary for muscle function, fertilization, and blood clotting, among other things. Because calcium is so critical, the cell regulates it tightly. Mitochondria play a part in this by quickly absorbing calcium ions and holding them until they are needed. Other roles for calcium in the cell include regulating cellular metabolism, steroid synthesis, and hormone signaling.

Heat production

When we are cold, we shiver to keep warm. But the body can also generate heat in other ways, one of which is by using a tissue called brown fat. During a process called proton leak, mitochondria can generate heat. This is known as non-shivering thermogenesis. Brown fat is found at its highest levels in babies, when we are more susceptible to cold, and slowly levels reduce as we age.

Mitochondrial disease

If mitochondria do not function correctly, it can cause a range of medical problems. The DNA within mitochondria is more susceptible to damage than the rest of the genome. This is because free radicals, which can cause damage to DNA, are produced during ATP synthesis. Also, mitochondria lack the same protective mechanisms found in the nucleus of the cell. However, the majority of mitochondrial diseases are due to mutations in nuclear DNA that affect products that end up in the mitochondria. These mutations can either be inherited or spontaneous. When mitochondria stop functioning, the cell they are in is starved of energy. So, depending on the type of cell, symptoms can vary widely. As a general rule, cells that need the largest amounts of energy, such as heart muscle cells and nerves, are affected the most by faulty mitochondria. The following passage comes from the United Mitochondrial Disease Foundation:

“Because mitochondria perform so many different functions in different tissues, there are literally hundreds of different mitochondrial diseases. […] Because of the complex interplay between the hundreds of genes and cells that must cooperate to keep our metabolic machinery running smoothly, it is a hallmark of mitochondrial diseases that identical mtDNA mutations may not produce identical diseases.”

Diseases that generate different symptoms but are due to the same mutation are referred to as genocopies. Conversely, diseases that have the same symptoms but are caused by mutations in different genes are called phenocopies. An example of a phenocopy is Leigh syndrome, which can be caused by several different mutations. Although symptoms of a mitochondrial disease vary greatly, they might include:

loss of muscle coordination and weakness, problems with vision or hearing
learning disabilities, heart, liver, or kidney disease, gastrointestinal problems, neurological problems, including dementia, Other conditions that are thought to involve some level of mitochondrial dysfunction, include:

Parkinson’s disease, Alzheimer’s disease, bipolar disorder, schizophrenia
chronic fatigue syndrome, Huntington’s disease, diabetes & autism.

Cellular Respiration: Glycolysis, Krebs Cycle, Electron Transport Chain

Atp Production & Kreps Cycle :

The Krebs cycle uses the two molecules of pyruvic acid formed in glycolysis and yields high-energy molecules of NADH and flavin adenine dinucleotide (FADH2), as well as some ATP. The Krebs cycle occurs in the mitochondrion of a cell.

The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycleor the Krebs cycle– is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydratesfats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.[3][4] Even though it is branded as a ‘cycle’, it is not necessary for metabolites to follow only one specific route; at least three segments of the citric acid cycle have been recognized.

The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP.

In eukaryotic cells, the citric acid cycle occurs in the matrix of the mitochondrion. In prokaryotic cells, such as bacteria, which lack mitochondria, the citric acid cycle reaction sequence is performed in the cytosol with the proton gradient for ATP production being across the cell’s surface (plasma membrane) rather than the inner membrane of the mitochondrion. The overall yield of energy-containing compounds from the TCA cycle is three NADH, one FADH2, and one GTP.