Organismal and Cellular Stress Responses upon Disruption of Mitochondrial Lonp1 Protease.

Cells engage complex surveillance mechanisms to maintain mitochondrial function and protein homeostasis. LonP1 protease is a key component of mitochondrial quality control and has been implicated in human malignancies and other pathological disorders. Here, we employed two experimental systems, the worm Caenorhabditis elegans and human cancer cells, to investigate and compare the effects of LONP-1/LonP1 deficiency at the molecular, cellular, and organismal levels. Deletion of the lonp-1 gene in worms disturbed mitochondrial function, provoked reactive oxygen species accumulation, and impaired normal processes, such as growth, behavior, and lifespan. The viability of lonp-1 mutants was dependent on the activity of the ATFS-1 transcription factor, and loss of LONP-1 evoked retrograde signaling that involved both the mitochondrial and cytoplasmic unfolded protein response (UPRmt and UPRcyt) pathways and ensuing diverse organismal stress responses. Exposure of worms to triterpenoid CDDO-Me, an inhibitor of human LonP1, stimulated only UPRcyt responses. In cancer cells, CDDO-Me induced key components of the integrated stress response (ISR), the UPRmt and UPRcyt pathways, and the redox machinery. However, genetic knockdown of LonP1 revealed a genotype-specific cellular response and induced apoptosis similar to CDDO-Me treatment. Overall, the mitochondrial dysfunction ensued by disruption of LonP1 elicits adaptive cytoprotective mechanisms that can inhibit cancer cell survival but diversely modulate organismal stress response and aging.

Histone Demethylases ELF6 and JMJ13 Antagonistically Regulate Self-Fertility in Arabidopsis.

The chromatin modification H3K27me3 is involved in almost every developmental stage in Arabidopsis. Much remains unknown about the dynamic regulation of this histone modification in flower development and control of self-fertility. Here we demonstrate that the H3K27me3-specific demethylases ELF6 and JMJ13 antagonistically regulate carpel and stamen growth and thus modulate self-fertility. Transcriptome and epigenome data are used to identify potential targets of ELF6 and JMJ13 responsible for these physiological functions. We find that ELF6 relieves expansin genes of epigenetic silencing to promote cell elongation in the carpel, enhancing carpel growth and therefore encouraging out-crossing. On the other hand, JMJ13 activates genes of the jasmonic acid regulatory network alongside the auxin responsive SAUR26, to inhibit carpel growth, enhance stamen growth, and overall promote self-pollination. Our evidence provides novel mechanisms of self-fertility regulation in A. thaliana demonstrating how chromatin modifying enzymes govern the equilibrium between flower self-pollination and out-crossing.