Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. Here we show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt-sig-
22Mitochondria coordinate diverse functions within neurites, including signaling events for axonal 23 maintenance, and degeneration. However, less is known about the role of mitochondria in axon 24 development and maturation. Here we find that in maturing retinal ganglion cells (RGCs) in vivo, 25 axonal mitochondria increase in size, number, and total area throughout development. We 26 demonstrate through multiple approaches in vivo that the mechanism underlying these 27 mitochondrial changes are dependent on eye opening and associated neuronal activity, which can 28 be mimicked by brain derived neurotrophic factor (BDNF). We report downstream gene and 29 protein expression changes consistent with mitochondrial biogenesis and energetics pathways, and 30 present evidence that the associated transcripts are localized and translated at mitochondria within 31 axons in an activity-dependent manner. Together these data support a novel model for 32 mitochondrial-localized translation in support of intra-axonal mitochondrial dynamics and axonal 33 maturation. 34 35 42 of approximately 600-1500 proteins encoded in the nucleus 5-12 , yet mitochondria can be separated 43 down the axon by a meter or more from the cell body 13 . 44 3 45 As a result, such cells have evolved unique mechanisms for maintaining continuous 46 communication between mitochondria and the nucleus 14 . These include shuttling mitochondria 47 and their nuclear-encoded proteins up and down axons using motor proteins kinesins and 48 dyneins [15][16][17][18] . Transported mitochondria are also capable of undergoing fusion or fission with 49 neighboring mitochondria, acquiring or shedding genetic material and proteins 19 . Finally, new 50 mitochondria can also be assembled and packaged with nuclear and mitochondrial encoded 51 proteins, in a process known as mitochondrial biogenesis. This process takes place in the 52 perinuclear space and within axons, leading to increased numbers of mitochondria in neuronal 53 compartments [20][21][22] . Together these changes in mitochondrial localization, size and total cellular 54 volume are referred to as mitochondrial dynamics. 55 56 An additional mechanism implicated in supplying nuclear proteins to distal axonal mitochondria 57 is the transport and then local translation of RNA in axonal compartments (reviewed elsewhere 23 ). 58Interestingly, many investigations indicate that a consistent and major portion of axon-localized 59 transcripts encode nuclear proteins that regulate mitochondrial functions [24][25][26][27] . Additionally, 60 nuclear-encoded mitochondrial transcripts have been shown to physically localize on/in 61 mitochondrial membranes 28-32 , with further evidence suggesting that mitochondria can act as local 62 translation sites [33][34][35] . However, it is not yet known how such localization is regulated. Here we find 63 that developmental changes in axonal mitochondria are regulated by activity in vivo, and explore 64 associated regulation of mRNA expression and localization by activity in RGCs in vi...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.