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While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment., (© 2023. Springer Nature Limited.)

Mitochondria play central roles in maintaining cellular metabolic homeostasis, cell survival and cell death, and generate most of the cell's energy. Mitochondria maintain their homeostasis by dynamic (fission and fusion) and quality control mechanisms, including mitophagy, the removal of damaged mitochondria that is mediated mainly by the Pink1/Parkin pathway. Pink1 is a serine/threonine kinase which regulates mitochondrial function, hitherto many molecular mechanisms underlying Pink1 activity in mitochondrial homeostasis and cell fate remain unknown. Peptides are vital biological mediators that demonstrate remarkable potency, selectivity, and low toxicity, yet they have two major limitations, low oral bioavailability and poor stability. Herein, we rationally designed a linear peptide that targets Pink1 and, using straightforward chemistry, we developed molecular probes with drug-like properties to further characterize Pink1. Initially, we conjugated a cell-penetrating peptide and a cross-linker to map Pink1's 3D structure and its interaction sites. Next, we conjugated a fluorescent dye for cell-imaging. Finally, we developed cyclic peptides with improved stability and binding affinity. Overall, we present a facile approach to converting a non-permeable linear peptide into a research tool possessing important properties for therapeutics. This is a general approach using straightforward chemistry that can be tailored for various applications by numerous laboratories.

The production of singlet oxygen is typically associated with inefficient dissipation of photosynthetic energy or can arise from light reactions as a result of accumulation of chlorophyll precursors as observed in fluorescent (flu)-like mutants. Such photodynamic production of singlet oxygen is thought to be involved in stress signaling and programmed cell death. Here we show that transcriptomes of multiple stresses, whether from light or dark treatments, were correlated with the transcriptome of the flu mutant. A core gene set of 118 genes, common to singlet oxygen, biotic and abiotic stresses was defined and confirmed to be activated photodynamically by the photosensitizer Rose Bengal. In addition, induction of the core gene set by abiotic and biotic selected stresses was shown to occur in the dark and in nonphotosynthetic tissue. Furthermore, when subjected to various biotic and abiotic stresses in the dark, the singlet oxygen-specific probe Singlet Oxygen Sensor Green detected rapid production of singlet oxygen in the Arabidopsis (Arabidopsis thaliana) root. Subcellular localization of Singlet Oxygen Sensor Green fluorescence showed its accumulation in mitochondria, peroxisomes, and the nucleus, suggesting several compartments as the possible origins or targets for singlet oxygen. Collectively, the results show that singlet oxygen can be produced by multiple stress pathways and can emanate from compartments other than the chloroplast in a light-independent manner. The results imply that the role of singlet oxygen in plant stress regulation and response is more ubiquitous than previously thought.

Metastatic spread of cancer cells is the leading cause of mortality from cancer. Metastatic cancer cells must penetrate through several barriers to escape the primary tumor and gain entry into the bloodstream in order to spread to other tissues. It is believed that invasive cancer cells penetrate these barriers by forming specialized F-actin rich protrusions called invadopodia that localize matrix degrading activity to cell-substrate contact points. Invadopodia gain their protrusive ability by combining the physical force generated by actin polymerization with the chemical activity of matrix degradation. Accumulating data over the past few years have shed light on the molecular mechanisms as well as kinase signaling pathways that regulate the complex process of actin polymerization in invadopodia. Here we review some of these mechanisms, the signaling pathways that regulate this process, as well as the in vivo relevance of invadopodial structures. Understanding the mechanisms that govern invadopodia formation and function is an essential step in the prevention of cancer invasion and metastasis., (Copyright © 2012 Elsevier GmbH. All rights reserved.)