In wild-type C. reinhardti algae a protease called ClpP1 is responsible for removing unfolded proteins produced by stress (left). The loss of ClpP1 (right) leads to the accumulation of unfolded proteins in the chloroplast (dark green) triggering the cpUPR. This causes nuclear genes which encode factors that assist in protein folding (such as chaperones and proteases) to become upregulated. In order to monitor changes to cpUPR signaling, a fluorescent protein was put under the control of one of these factors (VIPP2), so that fluorescence could only be observed when cpUPR was induced. By inserting random mutations into the genome and screening for mutants no longer displaying the fluorescent reporter, Perlaza et al. were able to identify MARS1, a kinase involved in transmitting the cpUPR signal from the chloroplast to the nucleus. MARS1: mutant affected in chloroplast-to-nucleus retrograde signaling 1.