About Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

'Great Escape' Helps Uncover Autoimmunity

by Anjali Aryamvally on February 24, 2018 at 8:18 PM
Font : A-A+

'Great Escape' Helps Uncover Autoimmunity

The exact moment when DNA escapes out of the mitochondria during cell death was discovered and filmed by a study led by Professor Benjamin Kile from Monash University's Biomedicine Discovery Institute (BDI). The process was termed the 'Great Escape' moment and this may one day prove to be the crucial trigger for autoimmune diseases like arthritis.

The study, published today in the journal Science, involved major collaborators from the Walter and Eliza Hall Institute and the Howard Hughes Medical Institute's Janelia Research Campus in the US.

Advertisement


Mitochondria are the ultimate double agent; they are essential to keep cells alive, but when damaged, they can trigger the body's own immune system with potentially devastating consequences. Because the DNA inside mitochondria (mtDNA) has many similarities with bacterial DNA (they share common ancestry), the body reacts to its presence outside the mitochondria, or indeed, outside the cell, as if under attack from invading pathogens. It is a similar failure to distinguish 'self' from 'non-self' that underlies inflammatory and autoimmune diseases.

While the release of mtDNA is thought to contribute to autoimmune diseases such as lupus, how it escapes from the mitochondria has never been explained. Monash BDI researcher Dr Kate McArthur, while completing her PhD at the Walter and Eliza Hall Institute, used a revolutionary new microscope at the Janelia Research Campus in the US to capture the moment when mitochondria form a 'hernia' that balloons out of the mitochondria expelling the DNA into the rest of the cell.
Advertisement

The live-cell lattice light-sheet microscopy (LLSM) system developed by Nobel Prize winner Eric Betzig is a new technique that allows scientists to observe living cells at groundbreaking resolution. Dr McArthur travelled to the Janelia Research Campus in Virginia multiple times between 2015-2017, and remembers the moment when she witnessed, for the first time, the mitochondria actively expelling its DNA.

"As scientists, we are taught to be quite sceptical when we see something unexpected, so I think my initial reaction was 'no way...'

"It was only after I had carefully repeated the experiment many times that I began to realise what we had found," Dr McArthur said.

According to Professor Kile, when a cell commits suicide (a normal part of the human body's balancing act to control blood cell numbers), two proteins called BAK and BAX are triggered.

"What we witnessed - in real time - was these professional killer proteins opening up huge 'macropores' in the outer membrane of the mitochondria, leading the inner contents to herniate out, bringing the mtDNA with it," Professor Kile said.

"BAK and BAX deliver the 'kill shot' designed to permanently disable the cell. But in doing that, mtDNA is lost from the mitochondria. In essence, this is collateral damage, which, if it isn't controlled properly, triggers the immune system to drive pathological inflammation," he said.

The discovery was cemented by images captured by Monash University's Titan Krios cryo-electron microscope, currently the most advanced microscope for biological electron microscopy, and the Walter and Eliza Hall Institute's new lattice light-sheet microscope, custom built by collaborators in the Institute's Centre for Dynamic Imaging.

Professor Kile stressed that, in research, "fundamental discoveries such as this are rare, and this one has profound implications for the understanding of a wide range of autoimmune diseases and infections.

"This has been a brilliant collaboration - between Monash's Biomedicine Discovery Institute, the Walter and Eliza Hall Institute of Medical Research here in Melbourne and the Janelia Research Campus in the US - which has brought together cutting-edge technologies and first-class expertise to address questions that before now, had never been asked, and would have been impossible to answer," he said.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
What's New on Medindia
Prevent Hacking of Medical Devices: FDA Sounds Alarm
Black Water: Benefits and Uses
World Hypertension Day 2022 - Measure Blood Pressure Accurately, Control It, Live Longer!
View all
News Archive
Date
Category
Advertisement
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

Most Popular on Medindia

Daily Calorie Requirements The Essence of Yoga Nutam (400mg) (Piracetam) Color Blindness Calculator Indian Medical Journals Accident and Trauma Care Find a Doctor Calculate Ideal Weight for Infants Drug Interaction Checker Diaphragmatic Hernia

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use