Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with α v integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or α v integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.

Mitophagy, which selectively degrades mitochondria via autophagy, has a significant role in mitochondrial quality control. When autophagy selects mitochondria as a cargo, Atg32 is bound by Atg11. It is shown that the phosphorylation of Atg32, especially phosphorylation of Ser-114 on Atg32, mediates the Atg11–Atg32 interaction and mitophagy.

Background:The physiological importance of mitophagy in yeast has been largely unexplored. Results: Mitochondrial DNA deletion frequently occurs in mitophagy-deficient cells during nitrogen starvation because of overproduction of the reactive oxygen species from unregulated mitochondria. Conclusion: Mitophagy prevents excess reactive oxygen species production and mitochondrial DNA mutation. Significance: Our findings provide insight into mitophagy-related disorders such as Parkinson disease.

Abbreviations: 3-MA, 3-methyladenine; ATG, autophagy-related; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; ER, endoplasmic reticulum; FUNDC1, FUN14 Domain Containing 1; LC3, microtubule-associated protein 1 light chain 3; MAPK, mitogen-activated protein kinase; MEF, mouse embryonic fibroblast; MEK, MAPK-ERK kinase; MKK, MAP kinase kinase; PE, phosphatidylethanolamine; PINK1, PTEN-induced putative kinase protein 1; PTEN, phosphatase and tensin homolog; siRNA, short interfering RNA; SQSTM1, sequestosome 1; Tet, tetracycline.In cultured cells, not many mitochondria are degraded by mitophagy induced by physiological cellular stress. We observed mitophagy in HeLa cells using a method that relies on the pH-sensitive fluorescent protein Keima. With this approach, we found that mitophagy was barely induced by carbonyl cyanide m-chlorophenyl hydrazone treatment, which is widely used as an inducer of PARK2/Parkin-related mitophagy, whereas a small but modest amount of mitochondria were degraded by mitophagy under conditions of starvation or hypoxia. Mitophagy induced by starvation or hypoxia was marginally suppressed by knockdown of ATG7 and ATG12, or MAP1LC3B, which are essential for conventional macroautophagy. In addition, mitophagy was efficiently induced in Atg5 knockout mouse embryonic fibroblasts. However, knockdown of RAB9A and RAB9B, which are essential for alternative autophagy, but not conventional macroautophagy, severely suppressed mitophagy. Finally, we found that the MAPKs MAPK1/ERK2 and MAPK14/p38 were required for mitophagy. Based on these findings, we conclude that mitophagy in mammalian cells predominantly occurs through an alternative autophagy pathway, requiring the MAPK1 and MAPK14 signaling pathways.