A newly discovered cellular process enables mitochondria to repair localized damage and sustain their optimal function.
Mitochondria, often referred to as the “powerhouse of the cell,” rely on a recently uncovered recycling process that was identified by researchers at The Hospital for Sick Children (SickKids).
Mitochondria are small components within cells that perform numerous vital roles, including producing energy essential for cell health. Each mitochondrion consists of two membranes: an outer membrane and an inner membrane. The inner membrane is folded into structures called cristae, which hold the proteins and molecules necessary for energy production. Damage to these cristae can adversely affect the entire cell.
“Our study demonstrates, for the first time, that mitochondria can recycle localized damage by removing compromised cristae and then returning to normal functionality,” explains Dr. Nicola Jones, a Staff Physician and Senior Scientist in the Cell Biology program at SickKids, who led the research published in Nature.
The team believes that this mechanism is not only vital for mitochondrial health but could also serve as a potential target for diagnosing and treating diseases linked to mitochondrial dysfunction, such as infections, fatty liver disease, aging, neurodegenerative disorders, and cancer.
The process of mitochondrial recycling
Within cells, structures known as lysosomes operate as recycling facilities that can break down various types of molecular material. Utilizing advanced microscopy at the SickKids Imaging Facility, Dr. Akriti Prashar, a postdoctoral fellow in Jones’ lab and the paper’s first author, discovered that damaged cristae can push through the outer membrane of mitochondria, allowing the lysosome to engulf and dismantle them effectively.
The researchers named this innovative process VDIM formation, which stands for vesicles derived from the inner mitochondrial membrane. By eliminating damaged cristae via VDIMs, cells can prevent the spread of harm to other parts of the mitochondria and the cell as a whole.
“We believe that VDIMs may serve as a protective mechanism for cells against health issues that impact mitochondria, such as cancer and neurodegeneration,” Prashar adds.
Introducing VDIM formation
The research team, which includes scientists from the Francis Crick Institute and Johns Hopkins University, found that creating a VDIM involves multiple steps and molecules. Initially, a damaged crista sends out a signal that triggers a channel on a neighboring lysosome, allowing calcium to exit the lysosome. This calcium then activates another channel on the mitochondria’s outer membrane, forming a pore that enables the damaged cristae to escape into the lysosome for digestion – a phenomenon previously unobserved. By recycling just the damaged crista, mitochondria can maintain their regular functions.
“Comprehending this process provides valuable insight into how mitochondria remain healthy, which is crucial for everyone’s overall health and longevity,” says Prashar.
Future studies will investigate how modifying VDIM formation could help alleviate symptoms or even prevent health issues arising from underperforming or damaged mitochondria.
This research received funding from the Canadian Institutes of Health Research (CIHR) and a SickKids Restracomp fellowship.
