Proton-cation translocation in tumor cell mitochondria

Area of Science:

• Mitochondrial bioenergetics
• Cancer cell metabolism

Background:

• Mitochondria play a crucial role in cellular energy production by maintaining the transmembrane electrochemical proton gradient (delta microH+).
• Tumor cells often exhibit altered metabolic pathways, potentially affecting mitochondrial function.

Purpose of the Study:

• To investigate the capacity of tumor cell mitochondria to conserve the proton gradient compared to normal liver mitochondria.
• To identify the specific mechanisms underlying any observed differences in proton gradient conservation.

Main Methods:

• Isolation of mitochondria from Ehrlich ascites tumor cells, Morris hepatoma 3924A, and normal rat liver.
• Measurement of aerobic transmembrane electrochemical proton gradient (delta microH+), including delta pH and delta psi, in different ionic media (K+ and Na+).
• Assessment of mitochondrial membrane permeability and Na+ (K+)-H+ exchange system activity using passive swelling experiments and studies on submitochondrial particles.

Main Results:

• Mitochondria from Ehrlich ascites tumor cells showed proton gradient conservation capacity comparable to normal liver mitochondria in K+ medium.
• Morris hepatoma 3924A mitochondria exhibited decreased delta microH+ conservation, mainly due to a lower delta pH.
• Both tumor mitochondrial types displayed reduced aerobic delta pH in Na+ medium, while delta psi remained similar to controls, indicating enhanced Na+ permeability and Na+ (K+)-H+ exchange activity.

Conclusions:

• The reduced capacity of tumor mitochondria to conserve aerobic delta pH is attributed to an enhanced cyclic flow of Na+ across the mitochondrial membrane.
• This increased Na+ permeability and exchange activity in tumor mitochondria may contribute to altered cellular bioenergetics in cancer.