Mitochondrial Metabolism

Unlocking the secrets of mitochondria – the powerhouses of our cells

9 May 2022

Understanding how our cells use and convert the nutrients from the food we eat could not only help with tackling cardiovascular diseases and Type 2 diabetes, it could also provide new insights into neurological disorders says the Institute’s Professor Nigel Turner. Professor Turner joined the Institute late last year as the head of our new Cellular Bioenergetics Laboratory and is embarking on two projects that focus on energy production.

Delving into the biology of mitochondria

Mitochondria help convert the energy from our food, into energy that cells can use.

They are vital to our survival and are present in nearly all human cells, but when they become dysfunctional, they can contribute to a whole range of inherited and acquired diseases, including heart failure.

Professor Turner’s team is going to focus on a fundamental aspect of the biology of mitochondria. This will involve characterising the response of mitochondria to different types of stress that might result from a gene mutation or exposure to certain drugs.

“We are looking at the molecules that are released from cells where mitochondrial metabolism is impaired. We have a very speculative project about this idea and think that secreted factors from the cells experiencing mitochondrial stress may function to affect signaling and nutrient metabolism in other cells,” says Professor Turner.

“This project may have relevance for a range of disorders including cardiometabolic diseases and neurological disease, where we know that mitochondrial dysfunction is at least partially involved in the pathogenesis of those conditions. It’s kind of a fishing expedition to discover novel bioactive molecules, but it’s fun and exciting work.”

Understanding how cancer cells rewire our metabolism

Professor Turner and his team are also going to be looking at cancer cell metabolism, which at first glance sounds like an unusual fit for an Institute focusing on heart disease.

Professor Turner says: “It's very well recognised that cancer cells dramatically rewire their metabolism, because if you think about the main priority of a cancer cell, it wants to accumulate a lot of nutrients so that it can grow and proliferate uncontrollably.

“So these cells reprogram their metabolism to take up lots of nutrients and to channel the bulk of those nutrients not into the traditional energy generation pathways, but instead into biosynthesis pathways needed for growth.

“We’re working primarily in pancreatic cancer, trying to understand those metabolic changes that facilitate growth, but also other metabolic adaptations that might be involved in the development of chemotherapy resistance for instance, or in helping the cancer cells spread to another organ.

“If we can find a way to target and prevent these metabolic adaptations, we could render the cells more liable to be cured by chemotherapy. While this work focuses on cancer cells, some of the information we might derive from our studies could be highly relevant to developing potential therapeutic options for other diseases where cells undergo similar metabolic adaptations.”

Professor Turner plans to utilise the Institute’s cutting-edge Innovation Centre for many of his projects, including the mass spectrometer machines, which separate and measure thousands of molecules per minute based on the precise quantitation of their size (mass) and electrical charge.

“The specific techniques of the mass spec will allow us to profile metabolites, lipids or proteins in our experimental models. We will try out several interventions and see what happens to the levels of specific molecules to determine if there are changes in given metabolic pathways,” he says.