Neutron study reveals structural weaknesses in cancerous mitochondria
05 Aug 2026 - Stephanie Richardson
A team from the University of Windsor, Canada, has used neutron scattering to reveal nanoscale structural differences between mitochondria in healthy and cancerous cells. Their findings reveal that cancer reshapes these key cellular structures, creating vulnerabilities that could be targeted by future therapies. The work also demonstrates the potential of neutron techniques for studying complex biological systems in their native state.
Often described as the ‘powerhouse of the cell’, mitochondria are responsible for generating much of the energy required for cellular function. Beyond energy production, they play key roles in metabolism and cellular signalling.
Mitochondria are enclosed by two lipid membranes whose composition and organisation are critical to their function. These membranes help mitochondria adapt to changing conditions and regulate key biological processes.
One of these processes is apoptosis, or programmed cell death. During apoptosis, the mitochondrial membrane becomes permeable, allowing the release of molecules that commit the cell to death. In healthy tissue, apoptosis is carefully controlled and plays an important role in embryonic development and the removal of damaged or dysfunctional cells.
Cancer cells are able to evade these death signals. Their rapid growth places enormous demands on cellular machinery, including the production of mitochondrial membranes. As a result, cancer cells often incorporate lipids in a less controlled way, leading to abnormalities in the membrane structure. These weaknesses present an attractive target for new therapeutics.
One therapeutic candidate is pancratistatin (PST), a naturally derived compound that has previously been shown to target mitochondria in cancer cells and trigger apoptosis while leaving healthy cells largely unaffected. This selective activity suggests that understanding the differences between cancer-cell and healthy-cell mitochondria could help researchers develop new and more effective cancer treatments.
A team from the University of Windsor, Canada, set out to investigate these differences. Through the ISIS-Neutrons Canada partnership, the researchers used small-angle neutron scattering (SANS) at the ISIS Neutron and Muon Source. They complemented these measurements with neutron spin echo (NSE) spectroscopy at the Spallation Neutron Source at the Oak Ridge National Laboratory and cryo-electron tomography (cryo-ET) at the Diamond Light Source. Together, these techniques allowed the team to investigate cancerous and non-cancerous mitochondrial structure and mechanics, and how cancerous mitochondria respond to PST.
“What makes this work particularly exciting is that neutron scattering allowed us to study functioning mitochondria without introducing labels or dyes that can alter their behaviour,” said Stuart Castillo, lead author of the study and a PhD researcher at the University of Windsor. “We were able to observe nanoscale structural differences between healthy and cancerous mitochondria directly, helping us connect membrane composition, mechanics and biological function in a way that has been difficult to achieve before.”
What makes this work particularly exciting is that neutron scattering allowed us to study functioning mitochondria without introducing labels or dyes that can alter their behaviour.
Stuart Castillo, PhD researcher at the University of Windsor
Using the SANS2D instrument, the researchers examined the ultrastructure of mitochondrial cristae, the intricate folds of the inner mitochondrial membrane that are essential for normal function. These structures are particularly challenging to study because many conventional techniques rely on probes or dyes, which can themselves alter membrane organisation. SANS enabled the team to observe these structures directly and monitor how they changed in cancerous cells.
The experiments revealed clear differences between healthy and cancerous mitochondria. SANS measurements showed that healthy mitochondria exhibited a more ordered lamellar architecture, while cancerous mitochondria showed evidence of less ordered, nonlamellar membrane arrangements. Cryo-ET measurements confirmed these findings, revealing disorganised cristae networks in the cancer-cell mitochondria. Additionally, NSE measurements showed that mitochondrial membranes from cancer cells were softer than those from noncancerous cells, indicating a more flexible and disordered membrane structure.
PST had an even more dramatic effect. The researchers found that exposure to PST caused a near-complete loss of structural organisation in cancerous mitochondria, while having comparatively little effect on healthy mitochondria. Since the mitochondrial structure is closely linked to its function, these disruptions are thought to play a key role in triggering cell death
The findings highlight the unique capabilities of neutron techniques for biological research. “This is more than a cancer paper. It’s a glimpse of how neutron scattering can transform the way we investigate biological and living systems,” said Drew Marquardt, Associate Professor at the University of Windsor.
This is more than a cancer paper. It's a glimpse of how neutron scattering can transform the way we investigate biological and living systems.
Drew Marquardt, Associate Professor at the University of Windsor
While the precise molecular mechanism by which PST remodels cancerous mitochondria remains the subject of future experiments, this study provides direct evidence linking changes in lipid composition to changes in mitochondrial structure and mechanics. At a time when resistance to conventional chemotherapy is a major challenge, the work points to new ways of exploiting the structural vulnerabilities of cancer-cell mitochondria.
More broadly, the study demonstrates the power of neutron scattering as a label-free tool for probing biological structures and dynamics at the nanoscale, opening new opportunities to study mitochondria and other complex biological systems in their native state.
Read the full paper at ACS Bio & Med Chem Au (opens in a new tab)
