PMID- 33585443
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210217
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, 
      Cell Fate, and Female Fertility.
PG  - 596819
LID - 10.3389/fcell.2020.596819 [doi]
LID - 596819
AB  - The fate and proliferative capacity of stem cells have been shown to strongly 
      depend on their metabolic state. Mitochondria are the powerhouses of the cell 
      being responsible for energy production via oxidative phosphorylation (OxPhos) as 
      well as for several other metabolic pathways. Mitochondrial activity strongly 
      depends on their structural organization, with their size and shape being 
      regulated by mitochondrial fusion and fission, a process known as mitochondrial 
      dynamics. However, the significance of mitochondrial dynamics in the regulation 
      of stem cell metabolism and fate remains elusive. Here, we characterize the role 
      of mitochondria morphology in female germ stem cells (GSCs) and in their more 
      differentiated lineage. Mitochondria are particularly important in the female GSC 
      lineage. Not only do they provide these cells with their energy requirements to 
      generate the oocyte but they are also the only mitochondria pool to be inherited 
      by the offspring. We show that the undifferentiated GSCs predominantly have 
      fissed mitochondria, whereas more differentiated germ cells have more fused 
      mitochondria. By reducing the levels of mitochondrial dynamics regulators, we 
      show that both fused and fissed mitochondria are required for the maintenance of 
      a stable GSC pool. Surprisingly, we found that disrupting mitochondrial dynamics 
      in the germline also strongly affects nurse cells morphology, impairing egg 
      chamber development and female fertility. Interestingly, reducing the levels of 
      key enzymes in the Tricarboxylic Acid Cycle (TCA), known to cause OxPhos 
      reduction, also affects GSC number. This defect in GSC self-renewal capacity 
      indicates that at least basal levels of TCA/OxPhos are required in GSCs. Our 
      findings show that mitochondrial dynamics is essential for female GSC maintenance 
      and female fertility, and that mitochondria fusion and fission events are 
      dynamically regulated during GSC differentiation, possibly to modulate their 
      metabolic profile.
CI  - Copyright (c) 2021 Garcez, Branco-Santos, Gracio and Homem.
FAU - Garcez, Marcia
AU  - Garcez M
AD  - iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 
      Lisbon, Portugal.
AD  - Graduate Program in Areas of Basic and Applied Biology (GABBA), Universidade do 
      Porto, Porto, Portugal.
FAU - Branco-Santos, Joana
AU  - Branco-Santos J
AD  - iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 
      Lisbon, Portugal.
FAU - Gracio, Patricia C
AU  - Gracio PC
AD  - iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 
      Lisbon, Portugal.
FAU - Homem, Catarina C F
AU  - Homem CCF
AD  - iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, 
      Lisbon, Portugal.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - P40 OD018537/OD/NIH HHS/United States
PT  - Journal Article
DEP - 20210128
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7876242
OTO - NOTNLM
OT  - Drosophila melanogaster
OT  - differentiation
OT  - fertility
OT  - germ stem cell
OT  - mitochondrial dynamics
OT  - oogenesis
OT  - oxidative phosphorylation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/16 06:00
MHDA- 2021/02/16 06:01
PMCR- 2020/01/01
CRDT- 2021/02/15 06:11
PHST- 2020/08/20 00:00 [received]
PHST- 2020/11/30 00:00 [accepted]
PHST- 2021/02/15 06:11 [entrez]
PHST- 2021/02/16 06:00 [pubmed]
PHST- 2021/02/16 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.596819 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Jan 28;8:596819. doi: 10.3389/fcell.2020.596819. 
      eCollection 2020.