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Analysis of Brain Mitochondria Using Serial Block-Face Scanning Electron Microscopy
Published on: July 9, 2016
Changes in liver mitochondrial plasticity induced by brain tumor
Daniel Pouliquen1, Christophe Olivier, Emilie Debien
1Inserm, U601, Equipe Apoptose et progression tumorale, F-44000, Nantes, France. daniel.pouliquen@univ-nantes.fr
Background:
Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria.
Methods:
Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H2Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements.
Results:
The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation.
Conclusion:
This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation.
Insights
Brain tumors disrupt liver mitochondria water dynamics, altering membrane properties and leading to abnormal ion transport and cell death pathways. This highlights the liver's sensitivity to distant cancer effects.
Area of Science:
- Biophysics
- Cell Biology
- Oncology
Background:
- The liver is a key organ affected by systemic cancer effects.
- This study examines how chemically induced brain tumors impact liver mitochondria water dynamics.
Purpose of the Study:
- Investigate the effects of brain tumors on liver mitochondrial biophysical parameters.
- Analyze changes in water dynamics within liver mitochondria.
Main Methods:
- Induced central nervous system tumors in rats using ethylnitrosourea (ENU).
- Isolated liver mitochondria and measured water dynamics using Nuclear Magnetic Resonance (NMR).
- Calculated parameters for total water and macromolecule-associated structured water (H2Ost).
Main Results:
- Brain tumors caused a loss of water structural order in liver mitochondria.
- Increased membrane cholesterol content was observed, affecting bilayer permeability.
- Mitochondrial plasticity alterations impacted ionic exchanges, biogenesis, and caspase activation.
Conclusions:
- Liver mitochondria's structured water is sensitive to distant tumor development.
- Tumor-induced changes result in abnormal ion transport, mitochondrial biogenesis, and caspase activation.

