ABSTRACT
The genus Akebia belongs to the Lardizabalaceae family and comprises five species that are primarily distributed in East Asia. Plants of the Akebia genus comprise deciduous and semi-evergreen perennial twining vines that have been used in Chinese herbal medicine for at least 2000 years. The plants of this genus have the potential to form a novel forest crop with high nutritional and economic value because their fruit has a delicious sweet taste and rich nutrient components. In this study, we organized, analyzed, and evaluated the available published scientific literature on the botanical, ecological, and phytochemical characteristics of Akebia plants. Based on these studies, we briefly introduced botanical and ecological characteristics and focused on reviewing the development and utilization of wild genetic resources in the genus Akebia. We further explored the genus' rich nutritional components, such as triterpenes, flavonoids, polyphenols, polysaccharides, and fatty acids, and their potential use in food and health improvement applications. In addition, several papers describing advances in biotechnological research focusing on micropropagation, nutrient biosynthesis, and fruit ripeness were also included. This review provides comprehensive knowledge of the Akebia genus as a new forest crop for food and fruit utilization, and we also discuss future breeding and research prospects.
ABSTRACT
GLS1 orchestrates glutaminolysis and promotes cell proliferation when glutamine is abundant by regenerating TCA cycle intermediates and supporting redox homeostasis. CB-839, an inhibitor of GLS1, is currently under clinical investigation for a variety of cancer types. Here, we show that GLS1 facilitates apoptosis when glutamine is deprived. Mechanistically, the absence of exogenous glutamine sufficiently reduces glutamate levels to convert dimeric GLS1 to a self-assembled, extremely low-Km filamentous polymer. GLS1 filaments possess an enhanced catalytic activity, which further depletes intracellular glutamine. Functionally, filamentous GLS1-dependent glutamine scarcity leads to inadequate synthesis of asparagine and mitogenome-encoded proteins, resulting in ROS-induced apoptosis that can be rescued by asparagine supplementation. Physiologically, we observed GLS1 filaments in solid tumors and validated the tumor-suppressive role of constitutively active, filamentous GLS1 mutants K320A and S482C in xenograft models. Our results change our understanding of GLS1 in cancer metabolism and suggest the therapeutic potential of promoting GLS1 filament formation.