At BioAscent, we offer comprehensive bioenergetics and mitochondrial biology services, combining expertise in biochemistry, live-cell imaging, and functional metabolic assays, to support drug discovery. We spoke with expert Dr Yuxin Wu, who shared his insights into his role and work in mitochondrial research.

Can you describe your background in mitochondrial biology and your role at BioAscent?

My background spans over a decade of research across molecular biology, metabolic function, and integrated drug discovery. I completed my PhD at Queen's University Belfast and then undertook postdoctoral roles at Texas A&M University and Queen's University Belfast. During this period, I extensively utilised Seahorse bioenergetic assays to address complex scientific questions, specifically investigating liver metabolism in the context of diabetes research and exploring cell therapy-based tissue engineering for regenerative medicine.

At BioAscent, I am responsible for leading our mitochondrial research projects. A major part of my role involves overseeing our mitochondrial research pipelines, leveraging the Seahorse XF Pro platform to support our clients' drug discovery programs. I manage these client projects end-to-end; from drafting proposals and developing bespoke functional metabolic assays to budget management and final data reporting.

What capabilities does BioAscent have for studying mitochondrial biology, and how do you decide which assay is right for a given project?

At BioAscent, we possess a highly versatile and comprehensive suite of tools for investigating mitochondrial biology. On-site, our core bioenergetic profiling is driven by the Seahorse XF Pro platform, alongside our Incucyte® live-cell imaging system and advanced flow cytometry capabilities. Through our strategic partnership with world renowned mitochondria research expert Professor Kostas Tokatlidis at the University of Glasgow, we have direct access to their specialised mitochondrial research centre core facilities. This collaboration allows us to utilise high-content imaging, the Resipher platform and more, enabling us to address complex mitochondrial questions across multiple dimensions when a project demands it.

When deciding which assay is right for a given project, my approach is highly consultative. I begin by thoroughly analysing the client's specific goals and the exact scientific questions they need answered. From there, we co-design a tailored assay cascade. In most cases, the Seahorse assay serves as our powerful, foundational tool for assessing real-time metabolic function. However, because mitochondrial biology is so intricately linked to overall cell health, we frequently deploy other technologies to provide orthogonal assays. This complementary approach is critical for supplying clients with robust, multidimensional evidence regarding a compound's precise mechanism of action, its impact on metabolic reprogramming, and its cellular toxicity or cytoprotection profile.

What types of scientific questions are BioAscent scientists able to answer for our clients using mitochondrial assays?

Because mitochondrial function is central to both disease pathology and drug toxicity/protection, we can address a highly diverse range of scientific questions for our clients and provide a dynamic, comprehensive view of cellular metabolism.

Broadly, the questions we answer fall into three key categories:

• Mechanism of Action and Metabolic Reprogramming: Clients often need to know exactly how a compound alters cellular energy pathways, particularly in oncology or metabolic disease projects. We utilise the Seahorse XF Pro to definitively measure shifts between oxidative phosphorylation and glycolysis in real time, pinpointing the metabolic dependencies of specific cell types.

• Toxicity Profiling and Cytoprotection in Disease Models: While identifying early off-target mitochondrial liabilities is crucial, a significant portion of our work focuses on the inverse: demonstrating a drug candidate's protective effects. We routinely use the Seahorse XF Pro to model pathological disease states in vitro to assess whether a compound can preserve spare respiratory capacity, restore baseline mitochondrial function, or prevent metabolic collapse. We pair these bioenergetic readouts with continuous kinetic tracking on our Incucyte and High-Content live-cell imaging system to correlate metabolic protection with long-term improvements in cell health and survival.

• Deep Subcellular Dynamics and Long-Term Shifts: For more complex mechanistic questions, we leverage our collaboration with the University of Glasgow. If a client needs to know how a drug affects mitochondrial network architecture (like fission and fusion events), we utilise high-content imaging. Furthermore, if a project requires tracking subtle metabolic shifts over extended, multi-day compound exposures, we use the Resipher platform to continuously monitor dissolved oxygen consumption directly within the incubator.

What are some of the most common challenges you encounter when studying mitochondrial function?

The most common challenge we encounter is establishing the precisely correct in vitro model to address a client's unique scientific question. Mitochondrial function is highly sensitive to its environment, meaning off-the-shelf, generalised assays rarely provide the insights our clients require.

This challenge typically presents itself in two distinct ways during our project planning:

• Isolating the Mechanism of Action (MoA): When clients need to investigate a compound's specific MoA, we must often move beyond standard protocols. This requires highly specific modulation of the assay medium, fine-tuning substrate availability, or rigorously optimising the timing and concentration of reagent administration. Isolating a singular metabolic pathway demands a highly controlled environment.

• Establishing Pathophysiological Relevance: When clients want to mimic a specific disease state in vitro, the main hurdle is building a model that accurately reflects the true biological microenvironment. Choosing the correct cell type and mimicking the exact stressor, whether it is nutrient deprivation, hypoxia, or a genetic mutation, is essential to prevent artefactual outcomes. If the cell model doesn't accurately reflect the disease's metabolic reality, the resulting data can be misleading.

Overcoming these challenges requires meticulous upfront planning, rigorous optimisation, and bespoke assay design. We invest significant time during the initial phases of a project to ensure the model we build will generate robust, reliable, and actionable data.

How does BioAscent’s approach differ from a typical CRO when it comes to mitochondrial biology projects?

What truly sets BioAscent apart from a typical CRO in terms of mitochondria research capabilities is our departure from a 'one-size-fits-all' testing mentality. We operate as a deeply integrated drug discovery partner.

We offer bespoke expertise rather than standard, rigid assay execution. While the Seahorse XF Pro platform is the undisputed gold standard for measuring mitochondrial bioenergetics, its true value is only unlocked when the assay is expertly tailored to the specific biological question at hand. We leverage our extensive experience to custom-design highly optimised protocols, built specifically around each client's unique needs.

Furthermore, we provide a highly comprehensive, one-stop solution. A typical CRO might run a standalone metabolic assay and simply hand over the raw data. At BioAscent, we understand that confident decision-making requires robust, multi-dimensional evidence. Therefore, we seamlessly integrate our core bioenergetic profiling with other advanced technologies to provide orthogonal metrics of mitochondrial function. By combining these complementary approaches, we deliver a complete, mechanistic picture of a compound's activity and safety/protection profiles.

What do you enjoy most about mitochondrial biology projects?

What I enjoy most is the collaborative problem-solving aspect and directly helping our clients find the definitive answers they need. Often, a client will come to us with a promising hit compound, but they need to know if it truly exhibits the expected biological effect in a translatable setting. Providing that validation is incredibly rewarding.

In other cases, clients already have a wealth of excellent data from other assays, but they are missing the metabolic piece of the puzzle. Being able to deliver those crucial mitochondrial outcomes to bridge the gap and make their scientific picture whole is a great feeling.

Delivering these insights gives me a profound sense of accomplishment. It reinforces that through our work at BioAscent, we are actively driving integrated drug discovery forward, making a real impact on therapeutic development, and ultimately helping to shape a healthier world.

Read more about mitochondrial biology at BioAscent here.