Effects of uncoupling of mitochondrial energy conservation on the ultradian clock-driven oscillations in Saccharomyces cerevisiae continuous culture

Abstract

Protonophores have several different perturbative effects on dissolved O 2 concentrations in continuous cultures of Saccharomyces cerevisiae. As well as uncoupling energy conservation from mitochondrial electron transport in vivo, they reset ultradian clock-driven respiratory oscillations and produce cell cycle effects. Thus, additions at low concentration (1.25 μM) of either m-chlorocarbonyl-cyanide phenylhydrazone (CCCP) or 5-chloro-3- t-butyl-2-chloro-4 1-nitrosalicylanilide (S 13) led to phase resetting of the 48 min ultradian clock-driven respiratory oscillations. At 2.5 μM CCCP or 4 μM S 13, transient inhibition of oscillatory respiration (for 5 h) preceded synchronisation of the cell division cycle seen as a slow (9 h period) wave that enveloped the 48 min oscillation. At still higher concentrations of CCCP (5 μM), the cell division cycle was prolonged by about 7 h, and during this phase, the respiratory oscillation became undetectable. The significance of these observations with respect to the time-keeping functions of the ultradian clock is discussed.