Harnessing STING Signaling and Natural Killer Cells Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Breast Cancer.

Homologous recombination deficiency (HRD) contributes to genomic instability and leads to sensitivity to PARP inhibitors (PARPi). HRD also activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-interferon pathway, highlighting the need to understand the impact of cGAS-STING-IFN signaling on PARPi efficacy. In this study, we analyzed a cohort of 35 breast cancer patient-derived xenografts and mouse-derived allografts.

Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs.

Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive.

The role of Djp1 in import of the mitochondrial protein Mim1 demonstrates specificity between a cochaperone and its substrate protein.

A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-span model protein Mim1, we performed a high-throughput screen in yeast.

A crucial role for Mim2 in the biogenesis of mitochondrial outer membrane proteins.

Most of the mitochondrial outer membrane (MOM) proteins contain helical transmembrane domains. Some of the single-span proteins and all known multiple-span proteins are inserted into the membrane in a pathway that depends on the MOM protein Mitochondrial Import 1 (Mim1). So far it has been unknown whether additional proteins are required for this process.

Multispan mitochondrial outer membrane protein Ugo1 follows a unique Mim1-dependent import pathway.

The mitochondrial outer membrane (MOM) harbors several multispan proteins that execute various functions. Despite their importance, the mechanisms by which these proteins are recognized and inserted into the outer membrane remain largely unclear. In this paper, we address this issue using yeast mitochondria and the multispan protein Ugo1.

Mitochondria can recognize and assemble fragments of a beta-barrel structure.

β-barrel proteins are found in the outer membranes of eukaryotic organelles of endosymbiotic origin as well as in the outer membrane of Gram-negative bacteria. Precursors of mitochondrial β-barrel proteins are synthesized in the cytosol and have to be targeted to the organelle. Currently, the signal that assures their specific targeting to mitochondria is poorly defined.

Signals in bacterial beta-barrel proteins are functional in eukaryotic cells for targeting to and assembly in mitochondria.

The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts harbor beta-barrel proteins. The signals that allow precursors of such proteins to be targeted to mitochondria were not characterized so far. To better understand the mechanism by which beta-barrel precursor proteins are recognized and sorted within eukaryotic cells, we expressed the bacterial beta-barrel proteins PhoE, OmpA, Omp85, and OmpC in Saccharomyces cerevisiae and demonstrated that they were imported into mitochondria.