A possible new role for ATM in maintaining healthy mitochondria

Research Project information

Researchers: Professor Mike Kastan and Dr. Adam Brown
Institute: 
Duke University, North Carolina, USA
Cost: 
$163,992 over 24 months
Start Date: 
March 2015

What are Mitochondria?

Mitochondria are tiny compartments found within cells. They perform different and important
functions to keep us healthy. They convert energy locked in food into energy that the cell can use.
Mitochondria are often referred to as the powerhouses of the cells. They generate the energy that
our cells need to do their jobs. For example, brain cells need a lot of energy to be able to
communicate with each other and also to communicate with parts of the body that may be far away,
to do this substances need to be transported along the cells, which needs lots of energy.

What are the researchers proposing to do?

Mike and Adam aim to understand why mitochondria are dysfunctional in cells lacking ATM (the
protein which is missing or not functioning completely in A-T), as well as how ATM helps cells
respond to metabolic stress.

Why?

Observations from the laboratory suggest that many of the symptoms in A-T may arise from mitochondrial dysfunction and an incorrect response to metabolic stress. Mitochondria are extremely important for numerous cellular processes including energy production and cell death, so it is not surprising that mitochondrial dysfunctional is associated with many diseases (for example, Parkinson’s and diabetes). Furthermore, the majority of cells affected in A-T (such as neurons) are highly dependent on mitochondrial energy production and susceptible to metabolic stress.

How will the research be done?

The team will address the project in two ways. The first will be to identify why cells lacking ATM have dysfunctional mitochondria. They will use various microscopy techniques to view mitochondria in cells from A-T patients under normal conditions and in response to metabolic stress. The second uses large-scale proteomics (the study of proteins, their structure and functions) to identify novel targets of ATM in response to metabolic stress.

How could it make a difference to the lives of those affected by A-T?

This study has the potential to shift our thinking from A-T being a disease that primarily results from abnormal DNA damage responses to thinking of A-T as a disease that primarily results from cells in A-T patients having dysfunctional mitochondria. In doing this, Mike and Adam hope to positively impact patients with A-T by identifying markers of symptom onset and/or progression and developing improved models for studying and treating A-T in the future.