BioAscent is proud to support the next generation of scientists through its long standing partnership with the University of Glasgow, which was strengthened further by the recent award of two prestigious PhD studentships from Medical Research Scotland. One of the researchers benefiting from this collaboration is PhD student Tora Gulstad, who is working at the interface of mitochondrial biology and cancer research.

Tora will benefit from the University of Glasgow’s world leading mitochondrial biology expertise under the supervision of Professor Kostas Tokatlidis, alongside mentoring from BioAscent’s experienced scientists and access to specialised mitochondrial biology capabilities as part of our integrated drug discovery platform.

In this blog, Tora shares an inside look at her PhD project and the science behind it.

“We’re delighted to support Tora’s research through our partnership with Professor Kostas Tokatlidis, bringing together BioAscent’s cutting-edge mitochondrial biology platform with the University of Glasgow’s world‑leading mitochondria centre.”

Yuxin Wu, BioAscent Senior Scientist and Tora’s Industrial Supervisor.

Why are mitochondria so important in human health?

Mitochondria are essential organelles that power eukaryotic cells and sustain numerous processes vital to human health. Originating from an ancient symbiosis, they retain their own DNA and a distinctive double‑membrane architecture. Beyond generating cellular energy, mitochondria regulate iron–sulphur cluster biogenesis, ion and lipid homeostasis, and programmed cell death – functions central to metabolism, tissue integrity, and disease prevention. Most mitochondrial proteins are encoded in nuclear DNA and must be imported through specialised pathways. Among these, the mitochondrial disulphide relay system is crucial for delivering and oxidatively folding proteins within the intermembrane space. Proper mitochondrial protein import is indispensable, as defects impair energy production, disrupt cellular homeostasis, and contribute to a wide spectrum of human disorders.

The Tokatlidis Host Lab made the seminal discovery of the mitochondrial disulphide relay system, and over the past 25 years has defined this pathway at molecular, structural, and mechanistic levels, elucidating the targeting peptides that guide substrate entry, the transient disulphide bond chemistry that drives folding, and the structural features that ensure substrate maturation and retention. A major contribution was the demonstration that the disulphide relay system is directly coupled to the mitochondrial electron transport chain: electrons generated during oxidative folding are transferred via upstream relay components to cytochrome c, linking mitochondrial protein biogenesis directly to respiration and energy production. This discovery fundamentally revised prevailing models by establishing protein folding as an electron‑flux‑integrated process rather than a standalone import mechanism.

Subsequent work from the Tokatlidis Host Lab revealed that this pathway plays central roles in iron homeostasis, redox balance, reactive oxygen species control, and the stability of respiratory complex I, positioning the disulphide relay system as a critical hub for mitochondrial and cellular health. Disruption of this pathway compromises mitochondrial proteostasis, with downstream consequences for bioenergetics and viability. This research has elevated the components of the disulphide relay system from obscure import factors to attractive therapeutic targets, including in cancer, where mitochondrial function and proteostasis are extensively rewired. Mitochondrial dysfunction is implicated in diverse human diseases, and mitochondrial respiration is now recognised as a major driver of tumour growth and metabolic reprogramming. Loss of mitochondrial DNA suppresses tumour formation, underscoring the organelle’s importance. A mitochondrial import factor has been found overexpressed in several cancers, correlating with tumour progression, recurrence, and poor prognosis, and influencing oxidative stress responses, respiratory chain function, and sensitivity to metabolic inhibitors. Because cancer types vary widely and many treatments suffer from toxicity and resistance, targeting altered mitochondrial metabolism – potentially by inhibiting mitochondrial biogenesis – may offer a novel strategy to limit tumour proliferation and enhance therapeutic responsiveness. This is an area where the Host Lab’s foundational discoveries provide unique insight and translational potential, even as the regulatory networks governing mitochondrial biogenesis and adaptation, particularly in cancer, remain only partially understood.

“I’m thrilled to be collaborating with BioAscent on my PhD project at the University of Glasgow. Having the opportunity to work in a world leading laboratory such as the Tokatlidis Host Lab has been an inspiring starting point for my doctoral research. Expanding this research to a more translational field with the unique advantages offered by BioAscent is truly a fantastic opportunity. I am deeply grateful to Medical Research Scotland for their support in making this work possible.”

Tora Gulstad, PhD Student, University of Glasgow.

How can we use mitochondrial mechanics to circumvent current therapeutic limitations?

Small‑molecule inhibitors targeting mitochondrial and immune‑related pathways have gained significant attention as potential cancer therapies. Compared with antibody‑based treatments, small molecules offer advantages such as better tissue penetration, oral bioavailability, and reduced immunogenicity. Current strategies focus on blocking intracellular enzymes and signalling components that suppress anti‑tumour immune responses or reinforce immunosuppressive conditions within the tumour microenvironment.

Several immune‑pathway targets have already progressed to clinical trials. However, predicting which patients will benefit remains challenging, as reliable biomarkers are often lacking and many signalling pathways are highly interconnected. In mitochondrial‑focused approaches, small molecules frequently target the electron transport chain, but this broad disruption affects overall cellular function and increases toxicity. These limitations highlight the need for more selective mitochondrial targets that could weaken tumour metabolism while minimising harm to healthy tissues.

“Through our in silico expertise, the BioAscent team is well-positioned to rapidly explore the complex structural biology of mitochondrial targets. By refining biological hypotheses through advanced computational modelling, we aim to drive more informed and efficient drug discovery. We are excited to collaborate with Tora and the University of Glasgow, applying our screening platforms to identify high-quality chemical leads for cancer targets.”

Angelo Pugliese, Associate Director of In Silico Discovery.

What will the project explore?

Mitochondria sit at the crossroads of metabolism, stress responses, and disease, making their protein‑import and regulatory pathways powerful therapeutic entry points. By selectively disrupting cancer‑associated mitochondrial adaptations – rather than the organelle as a whole – we open the door to treatments that weaken tumours while sparing healthy tissue. This project tackles an important gap in our understanding by focusing on the molecular machinery that drives mitochondrial production.

In this project we want to harness important new findings from the Host Lab to inform new drug discovery directions. In collaboration with BioAscent we aim to discover and refine small molecules that specifically inhibit a master regulator of mitochondrial biogenesis, which prepares the way for a new class of anti-cancer drugs. The collaboration allows us to combine in-silico screening with biochemical validation, which makes the approach both cutting-edge and efficient.

Learn more about BioAscent’s mitochondrial biology expertise here.