Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes.
Animals
Cell Proliferation
/ genetics
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ genetics
Enterocytes
/ metabolism
Gene Knockout Techniques
Homeostasis
Intestines
/ cytology
Janus Kinases
/ genetics
Longevity
/ genetics
MAP Kinase Kinase 4
/ genetics
Mitochondria
/ genetics
Mitochondrial Dynamics
Oxidation-Reduction
STAT Transcription Factors
/ genetics
Signal Transduction
/ genetics
Stem Cells
/ cytology
Transcription Factors
/ genetics
Tumor Suppressor Proteins
/ genetics
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
19
02
2020
accepted:
03
09
2020
revised:
27
10
2020
pubmed:
16
10
2020
medline:
1
1
2021
entrez:
15
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33057338
doi: 10.1371/journal.pgen.1009140
pii: PGENETICS-D-20-00223
pmc: PMC7591072
doi:
Substances chimiques
Clbn protein, Drosophila
0
Drosophila Proteins
0
STAT Transcription Factors
0
Transcription Factors
0
Tumor Suppressor Proteins
0
Janus Kinases
EC 2.7.10.2
hop protein, Drosophila
EC 2.7.10.2
MAP Kinase Kinase 4
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009140Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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