| Summary: | Our previous work revealed that the anabolism of <i>Monascus</i> secondary metabolites is closely related to cofactor metabolism. In this study, we have further investigated the regulation mechanisms of respiratory complex I in response to the cell growth and secondary metabolite biosynthesis of <i>M. purpureus</i>. The results showed that downregulating the mRNA level of gene <i>ndufs</i>8 in <i>M. purpureus</i> sharply increased the secondary metabolites biosynthesis, cell growth and glucose consumption rates at the fermentation metaphase; slightly increased the colony diameter and biomass, and dramatically changed the mycelia morphology; and decreased the tolerances to environmental factors (especially H<sub>2</sub>O<sub>2</sub>). It also significantly inhibited the enzymes activities of respiratory complex I, III and superoxide dismutase, but stimulated that of complex II, IV and peroxidase, leading to an increase in reactive oxygen species (ROS) level and a decrease in ATP concentration. Furthermore, transcriptome analysis revealed that the mRNA levels of genes involved in respiratory chain, tricarboxylic acid cycle, and fatty acid degradation were downregulated, but those in the citrinin and <i>monascus</i> pigment biosynthesis and related pathways were upregulated. These data revealed that complex I plays a vital role in regulating the cell growth and secondary metabolism of <i>Monascus</i> via changing the intracellular ROS and ATP levels.
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