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Oxidative phosphorylation properties of mitochondria isolated from transplanted hepatoma
Abstract:
Mitochondria were isolated from Morris hepatomas with rapid (types 3683, 7777, and 3924A) and intermediate (types 5123D and 7800) growth rates, using proteolytic digestion of minced tumor tissue to release the particles. Mitochondria isolated by the same procedure from rat liver were employed as controls. All the hepatoma mitochondria were capable of coupled respiration with normal phosphorylation yields (ADP/O) and respiratory control ratios ranging from 2 to considerably more than 10. Particles from hepatomas 7777 and 7800 exhibited properties closest to liver mitochondria, while those from hepatomas 3683 and 3924A showed the greatest difference. All the hepatoma mitochondria were capable of oxidizing succinate, 3-hydroxybutyrate and monoamines. However, the oxidation rates of the latter two substrates by mitochondria from hepatomas 3683 and 3924A were only a fraction of the control rates. These differences appeared to be due, at least in part, to the structural instability of the isolated hepatoma mitochondria. In contrast to the reports of others, all hepatoma mitochondria exhibited considerable stimulation of ATPase activity by uncouplers. Maximal stimulation of ATPase activity by representatives of three classes of uncouplers was in all instances comparable to the values obtained for rat liver mitochondria.
Insights
Mitochondria from Morris hepatomas show varying respiratory functions and ATPase activity. Rapidly growing hepatoma mitochondria exhibit reduced substrate oxidation rates, potentially due to instability.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Mitochondria play a crucial role in cellular energy metabolism.
- Dysfunctional mitochondria are implicated in cancer development and progression.
- Morris hepatomas provide a model for studying mitochondrial alterations in cancer.
Purpose of the Study:
- To investigate the functional and structural properties of mitochondria isolated from Morris hepatomas with different growth rates.
- To compare mitochondrial function in hepatomas with that of control rat liver mitochondria.
Main Methods:
- Isolation of mitochondria from Morris hepatomas (types 3683, 7777, 3924A, 5123D, 7800) and rat liver using proteolytic digestion.
- Assessment of coupled respiration, phosphorylation yields (ADP/O), and respiratory control ratios.
- Evaluation of substrate oxidation rates (succinate, 3-hydroxybutyrate, monoamines).
- Measurement of ATPase activity and its stimulation by uncouplers.
Main Results:
- All hepatoma mitochondria maintained coupled respiration with normal phosphorylation yields and respiratory control ratios.
- Mitochondria from intermediate growth rate hepatomas (7777, 7800) showed properties closest to liver mitochondria.
- Mitochondria from rapid growth rate hepatomas (3683, 3924A) exhibited reduced oxidation rates for 3-hydroxybutyrate and monoamines, possibly due to structural instability.
- All hepatoma mitochondria displayed significant ATPase stimulation by uncouplers, comparable to liver mitochondria.
Conclusions:
- Mitochondrial respiratory function is altered in Morris hepatomas, with variations depending on growth rate.
- Structural instability may contribute to impaired substrate oxidation in rapidly growing hepatoma mitochondria.
- Hepatoma mitochondria retain functional ATPase activity responsive to uncouplers, similar to normal liver mitochondria.