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Decreased mitochondrial function in UVA-irradiated dermal fibroblasts causes the insufficient formation of type I collagen and fibrillin-1 fibers

      Highlights

      • UVA irradiated fibroblasts form insufficient dermal fibers.
      • The ratio of extracellular versus intracellular fiber proteins is decreased by UVA.
      • Intracellular ATP levels in fibroblasts decrease immediately after UVA irradiation.
      • Mitochondrial quality in UVA-exposed fibroblasts decreases due to MITOL depletion.
      • Knockdown of MITOL in fibroblasts decreases the production of dermal fibers.

      Abstract

      Background

      Decreases of collagen fibers and the disappearance of oxytalan fibers are typical symptoms of photoaged skin. Although a low quality of mitochondria (MT) in photoaged skin cells has been observed, it is unknown whether the decreased quality of MT is responsible for the insufficient formation of dermal fibers.

      Objective

      To identify the role of mitochondrial quality in skin photoaging focusing on the formation of dermal fibers.

      Methods

      Type I collagen and fibrillin-1 fibers in normal human dermal fibroblasts (NHDFs) were observed by immunostaining. Type I collagen and fibrillin-1 proteins in NHDFs were quantified by ELISA. Mitochondrial quality was evaluated by measuring levels of intracellular ATP and MITOL, which regulate mitochondrial quality.

      Results

      UVA-irradiated NHDFs formed insufficient type I collagen and fibrillin-1 fibers and had a decreased ratio of extracellular versus intracellular levels of those proteins. Although expression levels of motor proteins that transport those proteins intracellularly were not affected by UVA, intracellular ATP levels, which is the driving force of motor proteins, were decreased by UVA along with decreased MITOL protein. Knockdown of MITOL in NHDFs decreased the level of intracellular ATP and caused the insufficient formation of type I collagen and fibrillin-1 fibers due to interfering with the secretion of those proteins.

      Conclusion

      These results indicate that a low quality of MT with ATP depletion in dermal fibroblasts caused by irradiation with UVA induces the insufficient formation of type I collagen and fibrillin-1 fibers due to the decreased extracellular secretion of those proteins.

      Abbreviations:

      MT (mitochondria), ATP (adenosine triphosphate), Drp1 (GTPase dynamin-related protein 1), Mfn (mitofusin), MITOL (mitochondrial ubiquitin ligase), ROS (reactive oxygen species), DMEM (Dulbecco's modified Eagle's medium), FBS (fetal bovine serum), BSA (bovine serum albumin), ABTS (2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), NHDFs (normal human dermal fibroblasts), NMIIB (non-muscle myosin IIB), KIF5B (kinesin family member 5B), ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), MMP (matrix metalloprotease)

      Keywords

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