Mitochondrial DNA: What are mitochondria?

Mitochondria are tiny organelles found in nearly every cell of the human body. They play a vital role in energy production, converting the food we eat into the energy our cells need to function. Also known as the ‘powerhouse of the cell’, mitochondria are responsible for producing chemical energy called ATP (adenosine triphosphate), which is necessary for all biological processes within the body to occur. But did you know that these organelles have their own DNA? This DNA is known as mitochondrial DNA, and it plays a unique role in inheritance.

In the 1960s, scientists Margit Nass and Sylvan Nass discovered that mitochondria contain their own DNA during experiments with chicken embryos viewed under an electron microscope. This was a surprising finding, as it was previously thought that all of an organism’s genetic material was contained in the nucleus of the cell. The discovery of mitochondrial DNA led to a new understanding of how inheritance works.

This means that every living person actually has two separate and distinct genomes: the human nuclear DNA genome, which is linear in shape and contains more than 20,000 pairs of genes, and the mitochondrial DNA (mtDNA) genome, which is circular and only contains 37 genes, typically present at between 100 and 10,000 copies per cell on a cell type-specific basis.

Of these 37 genes that comprise the mitochondrial genome, only 13 genes provide all the necessary instructions to make enzymes that are essential to the formation of ATP through a process called oxidative phosphorylation. But the role of mitochondrial DNA doesn’t stop there. The remaining 24 genes of the mitochondrial DNA provide the instructions for making transfer RNA (tRNA) and ribosomal RNA (rRNA). These types of RNA are chemical cousins of DNA, and they play a vital role in assembling protein building blocks (amino acids) into functioning proteins.

Unlike nuclear DNA, which is inherited from both parents, mitochondrial DNA is only inherited from the mother. This is because the egg cell, which is much larger than the sperm cell, contains many more mitochondria than the sperm cell. Moreover, the mitochondria in sperm are degraded almost immediately after fertilization. When an egg and sperm cell combine to form an embryo, the sperm cell’s mitochondria are thus not passed on.

This unique pattern of inheritance has important implications for genetics and medicine. For example, mutations in mitochondrial DNA can lead to a wide range of diseases, many of which are inherited exclusively through the maternal line.

What is Mitochondrial Inheritance?

The most peculiar thing about MtDNA is the fact that this DNA is maternally inherited – males and females inherit a copy of MtDNA from their mothers. Nuclear DNA, on the other hand, is inherited equally from both parents; a child will inherit 50% of their nuclear DNA from the mother and the other 50% from their father.

An mtDNA copy is passed down entirely unchanged through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. Mitochondrial inheritance is non-Mendelian, meaning it does not conform to the Mendelian laws of inheritance.

This mode of inheritance is called matrilineal or mitochondrial Inheritance. There are mitochondrial DNA testing services available that can help determine maternal lineage or whether the people tested share the same maternal line. Lineage DNA testing using MtDNA is ideal for testing ancient biogenetic origins and tracing one’s unique lineage. For instance, scientists have used MtDNA to compare the DNA of living humans of diverse origins in order to untangle evolutionary trees. MtDNA analyses suggest humans originated in Africa and can trace their maternal ancestry back to a single woman, who lived in Africa around 200,000 years ago. This woman is often referred to as “Mitochondrial Eve.”

In extremely rare cases, it may be possible for children to inherit mitochondrial DNA from their fathers. In 2018, geneticists led by Taosheng Huang from the Cincinnati Children’s Hospital Medical Centre reported the case of a four-year-old boy who showed signs of a mitochondrial disorder. When Huang and colleagues tested the boy, they were shocked to find that his mitochondrial DNA also seemed to contain paternal contributions, which left everyone scratching their heads. But when the boy’s sister and mother showed evidence of the same heteroplasmy (the co-existence of multiple mitochondrial DNA variants in a single source), Huang knew this situation wasn’t a simple error of measurement.

Later, the researchers three unrelated multi-generation families (17 individuals) with mtDNA heteroplasmy, ranging from 24% to 76%. This phenomenon may be present in as many as 1 in every 5,000 people, according to the preliminary investigation published in PNAS. However, in the overwhelming of cases, mtDNA is inherited solely from the mother’s side.

Mitochondrial Diseases

If there are any abnormalities in the mother’s mitochondria, they will be inherited by her offspring but if the father has abnormal mitochondria, he will not pass on the defect to his children since males do not pass on their MtDNA. Defects in mitochondrial DNA can cause cellular malfunctions and even cellular death. The areas that are mainly affected by mtDNA diseases include the brain, heart, liver, skeletal muscles, kidney, and the endocrine and respiratory systems.

Around 15% of mitochondrial diseases are due to mutations in the mitochondrial DNA itself. These mutations can arise due to any number of external factors like exposure to harmful radiation, toxins, and smoking, or due to internal mix-ups by the cell.

Since mitochondria are present in all types of cells, except red blood cells, a defect in one type of mitochondrial gene may produce an abnormality in the brain whereas, in another individual, it may produce a disease in the kidneys.

Some of the most well-known diseases caused by these mutations include Leber’s hereditary optic neuropathy and myoclonic epilepsy with ragged-red fibers. These diseases can be debilitating and even fatal. Other diseases include abnormalities of the muscles in the gastrointestinal tract, limbs, heart, lungs, etc. Since mitochondria are so widespread in the body and control incredibly diverse functions, the diseases of the mitochondria are just as diverse. Researchers are working on developing treatments for these diseases, but they are a complex set of disorders and much more research is needed.

Mitochondria are much more than just the powerhouses of the cell. They have their own DNA, known as mitochondrial DNA, which plays a unique role in inheritance. This DNA can be used to understand both our ancestry and the evolution of different species. It also has important implications for medicine, as mutations in this DNA can lead to a wide range of diseases. With continued research, we can hope to understand and treat these diseases.