'Selfish' Mutant Mitochondria Linked To A Range Of Diseases

Mitochondria, shown in red. Credit: NICHD/U. Manor

Mitochondrial dysfunction is a clear contributor to the aging process, and new research suggests certain mutations can create 'selfish' mitochondria - producing harmful behaviour and enabling evasion of cellular checks

As one of the primary hallmarks of the aging process, mitochondrial dysfunction is linked to a large group of conditions and age-related diseases. Exactly how these issues emerge however hasn't always been clear. Research is now confirming previous theories that some of the most insipid mutations are those that allow mitochondria to escape cellular quality check mechanisms, and persist to act in self interest. 

"Once we know the mechanisms that mutant mitochondria use to evade cellular regulation, then we can develop drugs that target these pathways and prevent the mutations from spreading" 

The interaction between mitochondria and their host cell is dynamic - with any given population of mitochondria in constant flux in response to their environment. More are created if there is a perceived deficit in energy, and many can be torn down if the cells senses any peculiarities. damaged mitochondria spill out a number of molecules that can trigger apoptosis for example as a protective response. 

There are two main ways mitochondria can slip through the net

The cell has a method of counting the number of mitochondrial genomes present in itself, which provides feedback on energy producing capability for example. On research on mitochondrial disorders in the model organism C. elegans, scientists discovered that particular types of mutations render mitochondria invisible to this counting process. This means there can be a perceived energy deficit, and the cell attempts to compensate by producing more mutant mitochondria - worsening the situation. 

Cells also have a process called the mitochondrial unfolded protein response, which aims to repair damaged and dysfunctional mitochondria while protecting them from being recycled altogether. When this process is activated it can also allow certain sly individuals to avoid destruction. This effectively means the mutant variants aren't being eliminated when they should be. 

Mitochondrial mutations are linked to a large number of diseases and conditions. Credit: Maulik Patel, Vanderbilt University

A link to aging

While initial theories on mitochondrial aging were focused on an increased production of free radicals, some scientists have suggested it's instead a slow, creeping accumulation of mutant mitochondria escaping regulatory mechanisms. This has an impact on energy production and creates wider dysfunction at the same time. This kind of process could feasibly lead to a gradual aging process, in which greater numbers of mutants begin to escape and build in certain cells. If we could find a way to either transfer vulnerable mtDNA to the nucleus (like the SENS Foundation are attempting to do) or target this evasion, we may be able to alleviate the dysfunction. 

"These are both cases where the mutant mitochondrial genomes exploit cellular defenses for their own 'selfish' interests"

Read more at MedicalXpress