ARC Centre of Excellence in Synthetic Biology

SYNTHETIC BIOLOGY

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23, Nov 2021

When does speed triumph over accuracy in cellular activity?

Is it better for the body to synthetise proteins slowly and surely or with speed and less accuracy?

That is one of the key questions in a new Aging Cell paper by Dr Tara Richman, of the Harry Perkins Institute in WA, and colleagues.

And it seems speed is better than accuracy when it comes to the effect on the heart and lifespan.

Many diseases are caused by dysfunction in the way proteins are produced within the mitochondria, the body’s energy factory.   In fact, 15 percent of all protein molecules have at least one amino acid error.

How much this impacts the body depends on the environment and the particular stressor.

One error-prone mutation, in a gene known as MRPS12, produces proteins at a faster rate but with lots of errors.  MRPS12 hyper accurate mutation produces proteins slowly but more accurately.

The research team created mouse models to understand the speed and accuracy of mitochondrial protein production in times of high stress – in this case a high fat diet.

“We found that both mutations are metabolically beneficial in reducing body weight and decreasing insulin and glucose intolerance, “ says Dr Richman, lead author of an international team that includes Centre Deputy Director Aleksandra Filipovska.

But there are impacts on specific tissues such as heart and liver. Overall, the researchers found that the rate of protein production is more important than accuracy.

“The error prone mice were protected from heart defects but had increased lipid accumulation in the liver,” says Dr Richman.

By contrast, the hyper accurate but slow mutation protects the liver but causes heart inflammation and reduced lifespan.

It’s hoped the improved understanding of mitochondrial mistranslation will lead to improvements in enzyme production for Australian industrial and molecular biotechnology.