Metabolic silencing induced by the small bacterial membrane protein YohP

Small membrane proteins represent an abundant and ubiquitous class of proteins that are often up-regulated when cells encounter unfavorable conditions, yet their function remains poorly understood. In bacteria, these proteins consist of typically less than 50 amino acids, without detectable catalytic activity. Thus, the benefit of producing these proteins during stress conditions is unknown. In the current study we used a multidisciplinary approach to determine the function of the 27-amino-acid-long protein YohP in Escherichia coli. Proteomics and lipidomics revealed that YohP production triggers the up-regulation of membrane protective proteins, increases the cardiolipin content, and leads to reduced membrane fluidity and a reduced membrane potential. Simultaneously, the stringent response is induced and many key metabolic enzymes are down-regulated. Overall, this multidisciplinary approach indicates that YohP-induced proteome and membrane changes initiate a state of metabolic silencing that protects E. coli against stress conditions and helps to conserve cellular resources.