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Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy
Maria Cavinato1,2, Ines Martic1,2, Sophia Wedel1,2
1Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
Abstract:
Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue. Mitochondria play an important role for the development of cellular senescence, in particular stress-induced senescence of human cells. However, many aspects of mitochondrial physiology relevant to cellular senescence and extrinsic skin aging remain to be unraveled. Here, we demonstrate that mitochondria damaged by UVB irradiation of human dermal fibroblasts (HDF) are eliminated by NIX-dependent mitophagy and that this process is important for cell survival under these conditions. Additionally, UVB-irradiation of human dermal fibroblasts (HDF) induces the shedding of extracellular vesicles (EVs), and this process is significantly enhanced in UVB-irradiated NIX-depleted cells. Our findings establish NIX as the main mitophagy receptor in the process of UVB-induced senescence and suggest the release of EVs as an alternative mechanism of mitochondrial quality control in HDF.
Insights
UVB exposure damages skin cells, but NIX-dependent mitophagy eliminates damaged mitochondria, aiding cell survival. Extracellular vesicle release also helps control mitochondrial quality during skin aging.
Area of Science:
- Cellular Biology
- Dermatology
- Aging Research
Background:
- Skin aging results from intrinsic and extrinsic factors, with UVB exposure causing oxidative damage and DNA injury.
- Cellular senescence, marked by senescent cell accumulation, is a hallmark of skin aging.
- Mitochondria are crucial in cellular senescence, but their role in extrinsic skin aging requires further study.
Purpose of the Study:
- To investigate the role of NIX-dependent mitophagy in eliminating UVB-damaged mitochondria in human dermal fibroblasts (HDF).
- To explore the relationship between UVB irradiation, NIX, and the shedding of extracellular vesicles (EVs) in HDF.
- To elucidate mechanisms of mitochondrial quality control in the context of extrinsic skin aging.
Main Methods:
- UVB irradiation of human dermal fibroblasts (HDF).
- Assessment of NIX-dependent mitophagy and its role in cell survival.
- Analysis of extracellular vesicle (EV) shedding in response to UVB and NIX depletion.
Main Results:
- UVB-irradiated HDF eliminate damaged mitochondria via NIX-dependent mitophagy, which is vital for cell survival.
- UVB irradiation induces extracellular vesicle (EV) shedding in HDF.
- NIX depletion significantly enhances UVB-induced EV shedding, suggesting an alternative mitochondrial quality control pathway.
Conclusions:
- NIX is identified as the primary mitophagy receptor involved in UVB-induced senescence in HDF.
- Extracellular vesicle release emerges as a potential alternative mechanism for mitochondrial quality control in HDF under UVB stress.
- These findings offer new insights into cellular mechanisms underlying extrinsic skin aging and potential therapeutic targets.
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