Mitochondrial DNA may have strong influence on cellular metabolism and disease susceptibility

About 1.5 billion years ago, tiny visitors came to live inside the cells that later evolved into all plant and animal life including humans.

Those visitors were mitochondria, small organelles whose prominent role is producing 90 percent of the chemical energy cells need to survive. Evolutionarily speaking, humans, animals and plants are thus a combination of two organisms.

Mitochondria have their own DNA, but the 13 genes in human mitochondria along with DNA sequences for tRNAs, rRNAs and some small peptides are massively overshadowed by the 20,000 genes in the human nucleus. Nevertheless, these diminutive mitochondria may have a strong influence on cellular metabolism and susceptibility to metabolic diseases like heart failure or obesity, according to preliminary research by Scott Ballinger, Ph.D., professor of pathology at the University of Alabama at Birmingham.

"For 50 years, researchers have tried to find disease susceptibility using Mendelian genetics," Ballinger said while speaking about studies of the chromosomal genes in the cell nucleus. "But this explains only 10 percent of the reasons for susceptibility to disease."

The possible impact of mitochondrial DNA on disease susceptibility depends on two facts. First, all of a person's mitochondrial DNA comes from the mother, via her egg. This is distinct from the chromosomal genes in the nucleus, where, on average, half come from the mother and half from the father. Second, human mitochondrial DNA has evolved into distinct haplotypes, and each of these types has mitochondrial DNA variations that are inherited together. There are approximately 25 to 35 basic mitochondrial DNA haplogroups, and one of them is found in African populations and has many subtypes due the deep genetic diversity of that continent.

To investigate the impact of mitochondrial DNA, Ballinger and colleagues looked for changes in metabolism and nuclear gene expression when they exchanged mitochondrial backgrounds of strains of mice -- specifically those having different mitochondrial DNA sequences, and also having notable differences in susceptibility to diseases associated with metabolism.

After switching the mitochondrial DNA backgrounds, Ballinger and colleagues measured changes in body composition, metabolism and nuclear gene expression in fat tissue when mice switched from a low-fat chow diet to a high-fat diet.  

In the first report of its kind, they found that switching the mitochondrial genetic background had a significant impact on adiposity, whole body metabolism and nuclear gene expression in mice.

For example, gene expression in both visceral and subcutaneous fat was markedly changed between mice sharing the same nuclear genome but having different mitochondrial DNA backgrounds, when fed chow versus a high-fat diet. These changes ranged from 10- to 50-fold differences in the number of genes affected, and mitochondrial DNA background influenced whether the number of affected genes were increased or decreased. These studies also found that metabolic efficiency and percentage of body fat in the mice were impacted as well.

"These results are clearly consistent with the notion that different nuclear-mitochondrial genetic combinations influence metabolism, adiposity and gene expression in different ways," Ballinger said. "The overall implication of this work is that it can provide a new framework for understanding complex genetic disease susceptibility that both an individual's nuclear and mitochondrial genomes, in combination, can affect disease development. We are now trying to understand how the different combinations of nuclear and mitochondrial encoded genes interact to alter metabolism, and how this influences individual disease susceptibility."

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

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There's a better way to decipher DNA's epigenetic code to identify disease

A new method for sequencing the chemical groups attached to the surface of DNA is paving the way for better detection of cancer and other diseases in the blood, according to research from the Perelman School of Medicine at the University of Pennsylvania

These chemical groups mark one of the four DNA "letters" in the genome, and it is differences in these marks along DNA that control which genes are expressed or silenced.

Enzymes, rather than harsh chemical reactions, can be used to reveal the epigenetic code in DNA.
Credit: Rahul Kohli, Univeristy of Pennsylvania

To detect disease earlier and with increased precision, researchers have a growing interest in analyzing free-floating DNA in settings in which there is a limited amount, such as that extruded from tumors into the bloodstream.

"We're hopeful that this method offers the ability to decode epigenetic marks on DNA from small and transient populations of cells that have previously been difficult to study, in order to determine whether the DNA is coming from a specific tissue or even a tumor." said Rahul Kohli, MD, PhD, Assistant Professor of Biochemistry and Biophysics, and Medicine.

For the last several decades, the major methods used to decipher the epigenetic code have relied on a chemical called bisulfite. While bisulfite has proven useful, it also presents major limitations: it is unable to differentiate the most common modifications on the DNA building block cytosine, and more significantly, it destroys much of the DNA it touches, leaving little material to sequence in the lab.

The new method described in this paper builds on the fact that a class of immune-defense enzymes, called APOBEC DNA deaminases, can be repurposed for biotech applications. Specifically, the deaminase-guided chemical reaction is able to achieve what bisulfite could do, but without harming DNA.

"This technological advance paves the way to better understand complex biological processes such as how the nervous system develops or how a tumor progresses," said Hao Wu, PhD, Assistant Professor of Genetics. 

Using this method, the team showed that determining the epigenetic code of one type of neuron used 1,000-times less DNA than required by the bisulfite-dependent methods. From this, the new method could also differentiate between the two most common epigenetic marks, methylation and hydroxmethylation.

"We were able to show that sites along the genome that appear to be modified are in fact very different in terms of the distribution of these two marks," Kohli said. "This finding suggests important and distinctive biological roles for the two marks on the genome."

We encourage researchers all around the globe to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment  ,Epigenetics and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019