Cancer cells modulate their metabolism to proliferate and survive under the metabolic stress condition, which is known as endoplasmic reticulum (ER) stress. Therefore, cancer cells should suppress ER stress-mediated cell death and induce autophagy—which recycles metabolites to provide energy and new macromolecules. In this study, we demonstrate that the ER membrane protein BAP31 acts to suppress adaptation to ER stress conditions, induce cell death, and suppress autophagy by forming a BAP31-STX17 protein complex. The loss of BAP31 stimulates tumor growth in metabolic stress conditions in vivo and enhances invasion activity. Therefore, BAP31 stimulates cell death and inhibits autophagy, and it can be considered a novel tumor suppressor factor that acts by preventing ER stress adaptation.

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Cell aging attenuates cellular functions, resulting in time-dependent disruption of cellular homeostasis, which maintains the functions of proteins and organelles. Mitochondria are important organelles responsible for cellular energy production and various metabolic processes, and their dysfunction is strongly related to the progression of cellular aging. Here we demonstrate that disruption of proteostasis attenuates mitochondrial function before the induction of DNA damage signaling by proliferative and replicative cellular aging. We found that lotus (Nelumbo nucifera Gaertn.) germ extract clears abnormal proteins and agglutinates via autophagymediated restoration of mitochondrial function and cellular aging phenotypes. Pharmacological analyses revealed that DAPK1 expression was suppressed in aging cells, and lotus germ extract upregulated DAPK1 expression by stimulating the acetylation of histones and then induced autophagy by activating the DAPK1-Beclin1 signaling pathway. Furthermore, treatment of aging fibroblasts with lotus germ extract stimulated collagen production and increased contractile ability in three-dimensional cell culture. Thus, time-dependent accumulation of abnormal proteins and agglutinates suppressed mitochondrial function in cells in the early stage of aging, and reactivation of mitochondrial function by restoring proteostasis rejuvenated aging cells. Lotus germ extract rejuvenates aging fibroblasts via the DAPK1-Beclin1 pathway-induced autophagy to clear abnormal proteins and agglutinates. www.aging-us.com 5 AGINGTable 1. List of plant extracts. No. Scientific name Part of plant Vitis vinifera L. Leaf Angelica keiskei (Miq.) Koidz. Leaf/Stem Uncaria gambir (W. Hunter) Roxb. Leaf/Scion Arnica montana L. Flower Ginkgo biloba L. Leaf Urtica dioica L. Leaf Artemisia capillaris Thunb. Flower Curcuma longa L. Rhizome Malva sylvestris L. Flower Camellia sinensis (L.) Kuntze Leaf Rosa multiflora Thunb. Fruit lsodonis japonicus (Burm.f.) H. Hara Leaf/Stalk Scutellaria baicalensis Georgi Root Phellodendron amurense Rupr. Bark Foeniculum vulgare Mill. Fruit Ononis spinosa L. Root Olea europaea L. Leaf Artemisia indica Willd. var. maximowiczii (Nakai) H. Hara Leaf Matricaria chamomila L. Flower Glycyrrhiza glabra L. Root Glycyrrhiza glabra L. Leaf Rubus idaeus L. Fruit Lonicera japonica Thunb. Flower Sophora flavescens Aiton Root Macroptilium atropurpureum (DC.) Urb. Flower/Leaf/Stem Alpinia speciosa (Wendl.) K. Schum. Leaf Gentiana lutea L. Rhizome/Root Oryza sativa L. Bran Punica granatum L. Pericarp Salvia officinalis L. Leaf Crataegus cuneata Siebold & Zucc. Fruit Gardenia jasminoides J. Ellis Fruit Rehmannia glutinosa Libosch. var. purpurea Makino Root Perilla frutescens (L.) Brijton var. crispa (Benth.) Leaf Paeonia lactiflora Pall. Root Sanguisorba officinalis L. Root Houttuynia cordata Thunb. Above-ground part Averrhoa carambola L. Leaf Centella asiatica (L.) Urb. Leaf/Stem Morus alba L. Root Ziziphus jujuba Mill. var. inermis (Bunge) Rehder Fruit Citrus unshiu (Swingle) Marcow. Peel Rubus chi...

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