Insight into mitochondrial dysfunction in ageing

A mechanism which controls mitochondria production activity has been identified, and could help explain mitochondrial functional decline with age.

Previously it was unknown how the mitochondria regulate the import and synthesis of proteins that it needs to respond to changes in the availability of certain metabolites. Now, researchers from the Buck Institute for Research on Ageing, Novato, California, have uncovered a protein called Tom70 which was known to control import of mitochondrial proteins into the mitochondria, also helps to coordinate this step with the synthesis of mitochondrial protein in the cell nucleus.

'We discovered a new function for this protein, and we provide a mechanism of how Tom70 can do good things to the cell' said, Dr Chuankai Zhou, lead author of the study, which is published in eLife.

A decline of mitochondrial function with age is associated with numerous chronic diseases, including cancer, diabetes, and obesity. But the reason for this decline is unclear.

Maintaining mitochondrial function depends on the continued production of new mitochondria in a process called mitochondrial biogenesis. This has two main steps: producing mitochondrial proteins, 99 percent of which come from nuclear DNA, and importing these into mitochondria. While these steps are well understood individually, little is known about how they coordinate to avoid a build-up of proteins outside mitochondria.

The authors hypothesised that the same proteins controlling import might also regulate protein synthesis. They discovered that by increasing the expression of Tom70, an import protein on the surface of mitochondria, they increased the expression of many mitochondrial proteins and mitochondrial DNA. By removing Tom70, they reduced the expression of many mitochondrial proteins.

The authors suggest the dual role of Tom70 allows it to match protein synthesis rates with import to avoid the accumulation of mitochondrial proteins outside mitochondria and coordinate mitochondrial biogenesis.

Tom70 has been shown to decline with age in yeast, flies, and human heart cells. The authors suggest this could play a key role in mitochondrial dysfunction observed in ageing. Dr Zhou hopes that the new understanding of Tom70 could open a different way to think about, mitigate and reverse that process.

Our research finding that the molecule Tom70 is coordinating both aspects [of mitochondrial biogenesis] bridges two separate fields of study,' said Dr Zhou. 'If our hypothesis proves to be true, it will naturally lead to products, such as supplements or drugs. It just takes time.'

In the meantime, Dr Zhou will continue researching Tom70 in yeast to better understand how it regulates gene expression.