Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes


Autoři: Zhaoxia Dai aff001;  Dong Li aff001;  Xiao Du aff001;  Ying Ge aff001;  Deborah A. Hursh aff003;  Xiaolin Bi aff002
Působiště autorů: The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China aff001;  School of Medicine, Nantong University, Nantong, China aff002;  Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America aff003;  College of Basic Medical Sciences, Dalian Medical University, Dalian, China aff004
Vyšlo v časopise: Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009140
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009140

Souhrn

Precise regulation of stem cell activity is crucial for tissue homeostasis. In Drosophila, intestinal stem cells (ISCs) maintain the midgut epithelium and respond to oxidative challenges. However, the connection between intestinal homeostasis and redox signaling remains obscure. Here we find that Caliban (Clbn) functions as a regulator of mitochondrial dynamics in enterocytes (ECs) and is required for intestinal homeostasis. The clbn knock-out flies have a shortened lifespan and lose the intestinal homeostasis. Clbn is highly expressed and localizes to the outer membrane of mitochondria in ECs. Mechanically, Clbn mediates mitochondrial dynamics in ECs and removal of clbn leads to mitochondrial fragmentation, accumulation of reactive oxygen species, ECs damage, activation of JNK and JAK-STAT signaling pathways. Moreover, multiple mitochondria-related genes are differentially expressed between wild-type and clbn mutated flies by a whole-genome transcriptional profiling. Furthermore, loss of clbn promotes tumor growth in gut generated by activated Ras in intestinal progenitor cells. Our findings reveal an EC-specific function of Clbn in regulating mitochondrial dynamics, and provide new insight into the functional link among mitochondrial redox modulation, tissue homeostasis and longevity.

Klíčová slova:

Cell differentiation – Cloning – DAPI staining – Drosophila melanogaster – Gastrointestinal tract – Homeostasis – Mitochondria – Stem cells


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