Gender-dependent response of liver mitochondria to hyperthermic treatment

Abstract

Hyperthermia is applied for cancer treatment although the underlying molecular mechanisms are not properly understood. Mitochondria are important transducers of signal leading to hyperthermic cell injury. We show that the response of liver mitochondria (LM) to hyperthermia is gender-dependent. Fever temperature activated state 3 respiration (V3) in LM from the female rat but strongly (by 26 percents at 41 C) inhibited V3 in male LM. Female LM V3 at 44 C was not different from that at 37 C; inhibition (by 14 percents) was induced only by 44 C (then V3 in male LM was inhibited by 39 percents). However, hyperthermia induced uncoupling was much stronger in female LM. The respiratory chain in male LM is more sensitive to hyperthermia than in female LM, but temperature induced increase in membrane permeability to ions is much larger in female LM. The difference is very obviously pronounced in the supra-physiological range of temperature (42-46oC) commonly used for hyperthermic cancer treatment. Our data imply that gender specific differences and the impact of temperature induced changes in the membrane structure are yet underestimated in the understanding of signaling networks that determine cellular elimination or survival under hyperthermic stress.