Researchers at the Crick, The Hospital for Sick Children (SickKids) and Johns Hopkins University have found that mitochondria depend on a newly discovered recycling mechanism in order to clear away damaged sections and continue functioning.

In addition to being essential to keeping mitochondria healthy, this mechanism could present a future target for the diagnosis and treatment of conditions characterised by mitochondrial dysfunction, including infection, fatty liver disease, ageing, neurodegenerative disease and cancer.

Mitochondria are tiny structures inside of cells that carry out a wide range of critical functions, including generating energy for all life processes.

Every mitochondrion has two layers of membranes. On the inner membrane, folds called cristae contain proteins and molecules needed for energy production. When cristae are damaged, this can negatively impact the entire cell.

In research published today in Nature, the team found that mitochondria can locate and remove damaged cristae.  

Using high resolution microscopy at the SickKids Imaging Facility to analyse mammalian cells, the team identified that a mitochondrion’s damaged crista can squeeze through its outer membrane. A lysosome – a structure which acts as a recycling centre to digest different kinds of molecular material – then engulfs the crista and breaks it down.

The scientists named this process VDIM (‘vesicles derived from the inner mitochondrial membrane’) formation.

Nicola Jones, Staff Physician and Senior Scientist in the Cell Biology program at SickKids and lead author of the study, said: 

Our research shows, for the first time, that mitochondria are able to recycle a localised injury, removing damaged cristae, and then function normally afterward.

To further outline the steps involved in VDIM, researchers at the Crick used electron microscopy and a technique which combines electron and light microscopy to see what was happening in the mitochondria at a high resolution.

The powerful imaging techniques showed that a damaged crista releases a signal that activates a channel on the nearby lysosome to allow calcium to flow out. Calcium then activates another channel on the outer membrane of the mitochondria, which forms a pore and allows the damaged crista to squeeze out.

Akriti Prashar, former postdoctoral fellow at the Crick and now at SickKids, who led the study, said: 

We believe that VDIMs could be a way of protecting cells from health conditions that affect mitochondria, such as cancer and neurodegeneration. Understanding this process gives us insight into how mitochondria stay healthy, which is important to everyone’s overall health and longevity.

Max Gutierrez, Group Leader of the Host-Pathogen Interactions Laboratory at the Crick, said: 

Removing only the damaged parts of mitochondria is a kind of quality control, making sure that the cell is working at maximum efficiency. A range of powerful microscopes allowed us to spotlight a process which hadn’t been seen before.

Future research will explore how altering VDIM formation could improve symptoms or even prevent health conditions caused by underperforming or damaged mitochondria.

Original story from The Hospital for Sick Children (SickKids).