Fluorescence Microscopy Journal Club

Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

by Grieco, J. P., Allen, M. E., Perry, J. B., Wang, Y., Song, Y., Rohani, A., ..., and Schmelz, E. M

Key Points

  • As ovarian cancer cells progress through different stages, (1) the ratio changes between proteins related to mitochondrial fusion and fission, (2) the balance of ROS in different cells shifts, and (3) mitochondrial morphology change and relocation can be seen; and
  • Visualization and analysis also revealed a reduction in the abundance and size of mitochondria inside cancer spheroids when the oxygen availability was reduced.


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Front. Oncol., 13 January 2021
DOI: 10.3389/fonc.2020.600113

Because mitochondrial morphology constantly changes and mitochondrial fragmentation has been observed in different diseases, investigating mitochondrial morphology and dynamics is a key focus of contemporary cancer research.

Ovarian cancer leads to a high death rate in women when it has progressed to an aggressive state. How the cancer cells adapt to a non-permissive and hypoxic environment is not clearly understood; understanding how mitochondrial morphology and dynamics changes in ovarian progression is important to provide possible targets for future treatment against ovarian cancer.

In this paper by Grieco et al. (2021), the authors investigated the change of mitochondrial morphology and dynamics for progressive ovarian cancer cells at different stages. Their work included results at molecular and at sub-cellular levels. Results at the molecular scale suggested a shift of ratios between proteins related to mitochondrial fusion and fission and a shifted balance of ROS in different cells. Results at sub-cellular level suggest mitochondrial morphology change and relocation. This was determined by comparing the shape, branch number, cristae morphology of mitochondria in cells at different cancer stages. The Vutara super-resolution microscope was used to image the fluorescently labelled mitochondria inside cancer spheroids. By grouping the localizations into a volume using cluster analysis in SRX software, the authors quantified mitochondrial size and found that the size of mitochondria was smaller in more aggressive cancer cells. They also used the Vutara to image mitochondria in different conditions, such as varied locations within a cancer spheroid, different individual cancer spheroids, and a range of oxygen levels. Visualization and analysis revealed reduction in abundance and size when the oxygen availability was reduced.

      KEY TERMS:

  • Cancer research, Mitochondrial morphology, Mitochondrial fusion and fission, Hypoxia, Uncoupling protein, Reactive oxygen species, Mitophagy