“There has never been a better time to be a mitochondriac!”

25.5.2018
Mitochondrial research is undergoing a renaissance in the field of biomedicine, says Assistant Professor Thomas McWilliams. No wonder, since mitochondrial dysfunction seems to be linked with a breathtaking array of diseases.

Thomas McWilliams, Assistant Professor (Tenure Track) and Academy of Finland research fellow, is intensely interested in mitochondrial signalling and organelle crosstalk.

“Mitochondria lie at the heart of cellular metabolism. These rod-like structures exist within our cells and form a highly dynamic, almost ‘social’ network. They interact intimately with other organelles and generate the chemical energy that sustains life,” describes McWilliams.

In addition to energy production, mitochondria fulfil many other vital functions, and serve as the genetic repository of our maternal lineage.

The central role of mitochondria in cellular metabolism means that their dysfunction usually spells serious trouble. Indeed, mitochondrial dysfunction has been linked with a breathtaking array of human diseases. These include rare inherited disorders in addition to more common idiopathic diseases such as neurodegeneration, diabetes and cancer.

Clever cells: quality control and recycling

Our cells have developed elaborate ways to sense mitochondrial damage and ensure the smooth running of these vital power plants. Such mitochondrial quality control processes and their regulation in tissues are of particular interest to McWilliams.

In essence, one system revolves around autophagy – literally meaning from the Greek word: “to eat oneself”. This is a sophisticated recycling mechanism that our cells can exploit to destroy toxic or unnecessary components. “At home, we dispose of our waste by carefully separating it into different categories. Likewise, our cells can selectively identify harmful components and eliminate them,” explains McWilliams.

McWilliams’ lab is driven to understand how cells exploit this recycling pathway for damaged mitochondria. Dubbed ‘mitophagy’– this is a specialised quality control process that detects, neutralises and destroys damaged mitochondria.

For a decade already, mitophagy has been the focus of intensive research efforts from many labs around the world.

“Classically, mitophagy has been studied in cell culture by using chemical triggers to stimulate the process. This approach has enabled a highly detailed molecular dissection of how cells eliminate damaged mitochondria in response to stress. I think this work has been really vital, as revealed valuable molecular links between Parkinson’s disease and mitochondrial damage” says McWilliams.

"My own research has exploited cutting edge tools to visualise when, where and how mitophagy is happening within tissues. We discovered that rather than being merely a stress response, mitophagy appears to be a constant process within our tissues. There are striking differences in mitophagy between organ systems, cell subtypes and even during foetal development. It’s a very complex process in vivo, and much work remains to reveal the range of molecular signals that modulate mitophagy in different scenarios.”

 “These findings have unearthed an entirely new landscape to explore. I recently returned from the leading international conference in our field, and it was exciting to see that what we are doing is at the forefront of this research.”

Waste management issues

If cells are unable to effectively dispose of damaged mitochondria, this will likely result in dysfunction that causes disease. However, McWilliams cautions against jumping to conclusions:

“Much more research is needed to understand these processes. We must be cautious about oversimplifying and linking cellular pathways to diseases whose underlying mechanisms may be highly complex. Fortunately, we now have the right tools to investigate mitophagy and its regulation in a very rigorous and systematic fashion.

He remains defiantly optimistic: ”There has never been a better time to be a mitochondriac!”

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