Hreniukh V. Peculiarities of bioenergetic processes in mitochondria of Nemeth-Kelner lymphoma cells

The peculiarities of bioenergetic processes in mitochondria of Nemeth-Kelner lymphoma cells (NK/Ly) have been investigated using polarographic method. For the first time the functionally active mitochondria of NK/Ly with coupled respiration and ATP synthesis were isolated. Oxygen uptake and rate of ADP oxidative phosphorylation in lymphoma mitochondria are clearly lower compared to equal parameters in both mouse and rat liver mitochondria. Mitochondrial suspension isolated from lymphoma and hepatic cells have been proposed to use as a target of anticancer drugs in tumor and normal cells. The well-known anti-tumor drug doxorubicin decreases the rate of respiration in the mitochondria of mouse lymphoma by 43.8%, but does not affect the coupling processes of respiration and oxidative phosphorylation. Newly developed drug Les 3506 show reducing effect on normal liver mitochondria decreasing both the rate of oxygen uptake by 36.1% in the State 3 (according to B. Chance) and rate of phosphorylation by 40.7%. To compare effects of anti-tumor drug on both lymphoma and liver mitochondria an antibiotic landomycine A has been used. This treatment reduces metabolic rate of respiration in State 3 in liver and lymphoma mitochondria and rate of oxidative phosphorylation in liver mitochondria when NAD-dependent substrate a-ketoglutarate is used. Bafilomicyne and NAADP lead to a decrease in metabolic rate in State 3 by 49.1% (bafilomicyne) and by 67.1% (NAADP) in lymphoma mitochondria without significant affect on liver mitochondria. Bafilomicyne with NAADP leads to complete uncoupling lymphoma mitochondria after (during) the synthesis of ATP in oxidation of a-ketoglutarate and succinate. Using the experimental lymphoma NK/Ly model it has been shown that polarography of isolated mitochondria can be used as a effective tool for study both peculiarities of tumor cellular metabolism and sensitivity of tumor energetic processes to the anticancer drugs. Key words: mitochondria, respiration, oxidative phosphorylation, NK/Ly, doxorubicin, landomycin, bafilomicyne, NAADP.