Since its discovery over 20 years ago, the protein PINK1 has been linked to Parkinson’s, and in particular early-onset Parkinson’s disease. But how this protein attached to mitochondria, and was switched on, remained a mystery.

Earlier this year the WEHI team, led by Prof David Komander and Dr Sylvie Callegari revealed for the first time the structure of PINK1 and how it attaches to damaged mitochondria to start the recycling process.

Dr Callegari said of the PINK1 mutation in Parkinson’s disease, “it’s like the recycling manager doesn’t turn up for work so the toxic elements from damaged mitochondria build up, eventually causing neurons to die.”

“Discoveries like this pave the way for precision medicines in Parkinson’s disease. It will allow us to develop drugs that target specific proteins to address particular genetic mutations,” said Dr Callegari.

“We are absolutely thrilled and honoured to win this award. Our discoveries of PINK1 are a testament to years of work and persistence from every member of the team.”

Parkinson’s disease affects over 200,000 Australians. It’s the world’s fastest growing neurological condition and has been linked to over 20 genes, with PINK1 being one of the most prominent.

While there are drugs to help control symptoms, of which there are nearly 40, there are no drugs to slow down or stop the progression of the disease.

Mitochondria are essential for cellular energy production and are present in the cells of all plants and animals.

In a healthy person, when mitochondria are damaged PINK1 attaches to them and signals for other proteins to recycle their contents. But in a person with Parkinson’s the recycling isn’t as effective because PINK1 has a mutation that prevents it from attaching to the mitochondria.

Finding ways to boost PINK1 or make it work properly is critical, because the contents of mitochondria are toxic to brain cells if they are not recycled correctly.

Head of WEHI’s Ubiquitin Signalling Division, Professor David Komander, said winning the Eureka Prize was a wonderful way to recognise the multi-disciplined team.

“The hope is that our discovery on PINK1, essentially how it can be switched on, will lead to a drug that has the ability stop the disease progression which will be life-changing for people with Parkinson’s,” said Prof Komander, who is a laboratory head in the WEHI Parkinson’s Disease Research Centre.

“By recognising the impact of our work, this prize inspires us to keep progressing our research into understanding Parkinson’s disease and ultimately finding a cure.”

Even though the path to new drugs is complicated, the information the team uncovered is already being used by pharmaceutical companies to inform their Parkinson’s drug discovery programs.

Dr Callegari said the team’s long-term goal was to have a drug to slow down or stop the progression of Parkinson’s disease in clinical trials.

“Now we know exactly what PINK1 looks like and how it binds to mitochondria the path to finding drugs that boost PINK1 activity in people with Parkinson’s has some important signposts guiding the way,” she said.

This work was funded by National Health and Medical Research Council, The Hugh Christopher Middendorp Testamentary Trust and a CSL Centenary Fellowship.

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Header image L–R: Professor David Komander, Dr Nicholas Kirk, Dr Sylvie Callegari and Dr Alisa Glukhova.