Unlocking the mitochondrial genome: new research helps understand the impact of mitochondrial DNA diversity on metabolism and ageing

Mitochondria are the engines of our cells that convert the food we eat into energy. Mitochondrial dysfunctions linked to a number of health conditions can be associated with changes to the mitochondrial DNA sequence, but until now, these changes have been difficult to identify and analyse, mainly due to a lack of appropriate research methods, leaving the mitochondrial genome largely unexplored. NIHS scientists have developed a novel method that opens the door to the sensitive and accurate analysis of mitochondrial DNA, which will help in assessing the impact of its diversity on metabolism and ageing, and applying this knowledge to develop innovative nutritional concepts to maintain and improve health

Lausanne, Switzerland - 26 April 2017 - Mitochondria are the engines of our cells, converting the food we eat into energy. They have a small amount of their own DNA (mtDNA) separated from most of the cell DNA, which is packaged in chromosomes within the nucleus.

Mitochondrial dysfunction is linked to a number of pathological states, in particular related to metabolism, brain health and ageing. These dysfunctions can in some instances be associated with changes in the sequence of mtDNA, but variants are difficult to identify and analyse mainly due to a lack of appropriate research methods, leaving the mitochondrial genome largely unexplored.

First, each cell carries several hundred copies of the circular mitochondrial genome, so mutations may be present in just a subset of the mtDNA molecules, resulting in a heterogeneous pool of mtDNA (heteroplasmy). As a result, detecting and precisely quantifying variants requires extremely accurate tools. To further complicate identification, parts of the mitochondrial genome have been integrated into numerous copies within the nuclear genome over the course of evolution. These must be distinguished from genuine mtDNA sequences and excluded from any scientific analysis to avoid false or misleading results.

Building on strong expertise in the field as well as its genomics expertise, the Nestlé Institute of Health Sciences led by genomics scientist Julien Marquis has developed MitoRS (Mitochondrial DNA analysis by Rolling circle amplification and Sequencing) – a novel mtDNA sequencing strategy whose robustness, accuracy and sensitivity is demonstrated in a paper published today in an international peer reviewed scientific journal. 

This novel method allows the detection of variants with high accuracy and sensitivity, meaning the entire circular mitochondrial genome can be amplified (reproduced) in a single reaction using rolling circle amplification. This approach is easier to set up, quicker, less labour-intensive, requires much less DNA as a starting material, and is more cost-effective than the classical amplification method (PCR, polymerase chain reaction) used to generate thousands of copies of a particular sequence from a single segment of DNA. Fine-tuned parameters are then applied to allow detection of variants of the heterogeneous mtDNA pool even at low frequencies within a sample.

"Our MitoRS method combines a new level of accuracy and sensitivity to identify mtDNA variants. With its high throughput, ease of deployment and low costs, this technique opens the door to the systematic analysis of mtDNA variants in large-scale studies, helping assess in an unprecedented way the impact of mtDNA heterogeneity and its relationship with nuclear encoded genes on metabolism and ageing, two areas that are of key interest to us”, explains Patrick Descombes, Head of the Functional Genomics group at NIHS. “This method could also lead to the development of diagnostic tests to predict the risk of metabolic diseases, much like any of the genetic variants currently available.”

This work is aligned with the NIHS objective to better understand the complexity of metabolic health and ageing in a holistic and comprehensive way, starting at the molecular level, and apply this knowledge to then develop innovative nutritional concepts for the maintenance of health.

Did you Know...?

Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother. It is made of about 16 500 DNA building blocks (base pairs), representing just a small fraction of the total DNA in cells. Mitochondrial DNA contains 37 genes, all of them essential for normal mitochondrial function. A third of these genes provide instructions for making enzymes involved in generating adenosine triphosphate (ATP), the cell's main energy source.


About NIHS:

NIHS is a biomedical research institute, part of Nestlé’s global R&D network, dedicated to fundamental research aimed at understanding health and disease and developing science-based, targeted nutritional solutions for the maintenance of health. To achieve its aim, NIHS employs state-of-the-art technologies and biological models to characterise health and disease with a holistic and integrated approach. The ultimate goal of the Institute is to develop knowledge that can empower people to better maintain their health through nutritional approaches, especially in relation to their molecular profile and lifestyle status.


Marquis J, Lefebvre G, Kourmpetis YAI, Kassam M, Ronga F, De Marchi U, Wiederkehr A and Descombes P (2017). MitoRS, a method for high throughput, sensitive, and accurate detection of mitochondrial DNA heteroplasmy. BMC Genomics 18:326. https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3695-5

For enquiries, please contact:
Laura Camurri, Communications, NIHS

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