Mitochondrial disease, though once considered rare, now affects approximately 1 in 5,000 individuals, positioning it as the second most frequently diagnosed serious genetic ailment after cystic fibrosis. This condition remains relatively unfamiliar to most, despite its significant prevalence. Mitochondria are small, double-membraned organelles found in most living organisms’ cells, also called the “powerhouses of the cell,”. Mitochondria play a crucial role in producing energy for the cell’s various functions. Apart from energy production, mitochondria are involved in various other cellular processes, including regulating cell growth and death, calcium signalling, and metabolism. Symptoms for mitochondrial disease can range widely and may include: Muscle Weakness, Neurological Symptoms, Organ Dysfunction, Vision and Hearing Problems, Metabolic Disturbances and gastrointestinal Problems.
Researchers actively study mitochondrial diseases to better understand their underlying mechanisms and develop potential therapies. There’s also growing interest in the links between mitochondrial dysfunction and other conditions, like Alzheimer’s, Parkinson’s, diabetes, and certain cancers, which could offer new avenues for treatment and prevention.
Recent progress in imaging techniques has empowered researchers to attain remarkably high-resolution imagery of mitochondrial networks, unveiling their intricate functions. Imaging modalities like confocal, electron, light sheet microscopies have revealed the dynamic structure of mitochondria cristae in live cells, mitochondria interactome in a whole cell, transportation of cargo with neighbouring organelles. To quantify more complex aspects of mitochondrial network structure, such as associations with other organelles and subcellular neighbourhoods during specific cellular processes, an unbiased three-dimensional (3D) cellular mapping approach is required. Soft X-ray microscopy (SXT) is a powerful imaging technique that offers high-resolution visualization of biological samples, including subcellular structures like mitochondria.
The application of SXT allows for the mapping of cellular rearrangements during critical processes such as insulin secretion, stem cell development, and disease progression. SXT delivers unique information such as biochemical compositions or organelle molecular densities and enables impartial, label-free imaging of intact entire cells. Mapping mitochondria in the context of the cell’s near-native environment will offer more information about mitochondrial network functions.
SiriusXT has developed a laboratory-based soft X-ray microscope (the SXT-100) that allows researchers to image the whole internal structure of a cell, allowing the overall number, size and shape of organelles, such as mitochondria, to be accurately measured, without having to slice or stain the cell. This powerful instrument is now available as a laboratory instrument, increasing its flexibility, availability and utility for the disease and drug research community.
Mitochondria in various cell types imaged using the SXT-100. The top and bottom left panels depict long, branching mitochondria in HeLa cells, accompanied by a segmentation of mitochondria in the top right panel. The bottom-left panel displays a tomographic slice obtained with the SXT-100, featuring multiple mitochondria in a hepatic cell, and an overlay of the SXT-100 image with the light fluorescence of Mitotracker Green mitochondrial labelling.