Relationship between culture conditions and the dependency on mitochondrial function of mammalian cell proliferation

✍ Scribed by C. Van Den Bogert; J. N. Spelbrink; H. L. Dekker

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 812 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520323

✦ Synopsis

In cultured mammalian cells, the relationship was investigated between mito- chondrial function dnd proliferation under various culture conditions. Continuous inhibition of the expression of the mitochondrial genome was used to reduce the activity of enzymes involved in oxidative phosphorylation by 50% at every cell division. Under these conditions, culturing in relatively poor media resulted in arrest of the proliferation of most cell lines after 1 cell division. This was preceded by decreasing levels of ATP and increasing levels of ADP, suggesting that the ATP-generating capacity of the cells was limiting. Culturing in richer media led to arrest of the proliferation after 5 to 6 divisions, but accumulation of ADP was not observed. Addition of pyruvate to rich culture media and, at least for 1 cell line, increasing the CO, levels, completely prevented proliferation arrest. Inability to synthesise metabolic precursors via mitochondrial intermediary metabolism probably explains growth arrest of cells cultured in rich media. Pyruvate and C 0 2 were, however, without effect on the proliferation arrest of cells cultured in relatively poor media. Therefore, pyruvate dependency for growth of cells without functional mitochondria holds true only under culture conditions where the ATPgenerating capacib of the cells is not limiting. GI 1i192 WiIcv-Li$s, Inc.