Mitochondrial fission regulates germ cell differentiation by suppressing ROS-mediated activation of Epidermal Growth Factor Signaling in the Drosophila larval testis

被引:29
作者
Demarco, Rafael Senos [1 ]
Jones, D. Leanne [1 ,2 ,3 ]
机构
[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA
关键词
SELF-RENEWAL; METABOLIC-REGULATION; INSULIN-RESISTANCE; MARKED CLONES; PROLIFERATION; MAINTENANCE; DYSFUNCTION; PATHWAY; GENE; EGFR;
D O I
10.1038/s41598-019-55728-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mitochondria are essential organelles that have recently emerged as hubs for several metabolic and signaling pathways in the cell. Mitochondrial morphology is regulated by constant fusion and fission events to maintain a functional mitochondrial network and to remodel the mitochondrial network in response to external stimuli. Although the role of mitochondria in later stages of spermatogenesis has been investigated in depth, the role of mitochondrial dynamics in regulating early germ cell behavior is relatively less-well understood. We previously demonstrated that mitochondrial fusion is required for germline stem cell (GSC) maintenance in the Drosophila testis. Here, we show that mitochondrial fission is also important for regulating the maintenance of early germ cells in larval testes. Inhibition of Drp1 in early germ cells resulted in the loss of GSCs and spermatogonia due to the accumulation of reactive oxygen species (ROS) and activation of the EGFR pathway in adjacent somatic cyst cells. EGFR activation contributed to premature germ cell differentiation. Our data provide insights into how mitochondrial dynamics can impact germ cell maintenance and differentiation via distinct mechanisms throughout development.
引用
收藏
页数:10
相关论文
共 43 条
  • [1] Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
    Amoyel, Marc
    Anderson, Jason
    Suisse, Annabelle
    Glasner, Johanna
    Bach, Erika A.
    [J]. PLOS GENETICS, 2016, 12 (01):
  • [2] Mfn2 is critical for brown adipose tissue thermogenic function
    Boutant, Marie
    Kulkarni, Sameer S.
    Joffraud, Magali
    Ratajczak, Joanna
    Valera-Alberni, Miriam
    Combe, Roy
    Zorzano, Antonio
    Canto, Carles
    [J]. EMBO JOURNAL, 2017, 36 (11) : 1543 - 1558
  • [3] The Nuclear Lamina Regulates Germline Stem Cell Niche Organization via Modulation of EGFR Signaling
    Chen, Haiyang
    Chen, Xin
    Zheng, Yixian
    [J]. CELL STEM CELL, 2013, 13 (01) : 73 - 86
  • [4] Tissue-specific TAFs counteract polycomb to turn on terminal differentiation
    Chen, X
    Hiller, M
    Sancak, Y
    Fuller, MT
    [J]. SCIENCE, 2005, 310 (5749) : 869 - 872
  • [5] Mitochondrial fusion regulates lipid homeostasis and stem cell maintenance in the Drosophila testis
    Demarco, Rafael Senos
    Uyemura, Bradley S.
    D'Alterio, Cecilia
    Jones, D. Leanne
    [J]. NATURE CELL BIOLOGY, 2019, 21 (06) : 710 - +
  • [6] Fuller Margaret T., 1993, P71
  • [7] SITE-SPECIFIC RECOMBINATION BETWEEN HOMOLOGOUS CHROMOSOMES IN DROSOPHILA
    GOLIC, KG
    [J]. SCIENCE, 1991, 252 (5008) : 958 - 961
  • [8] Genetic odyssey to generate marked clones in Drosophila mosaics
    Griffin, Ruth
    Binari, Richard
    Perrimon, Norbert
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (13) : 4756 - 4763
  • [9] GERMINAL PROLIFERATION CENTER IN THE TESTIS OF DROSOPHILA-MELANOGASTER
    HARDY, RW
    TOKUYASU, KT
    LINDSLEY, DL
    GARAVITO, M
    [J]. JOURNAL OF ULTRASTRUCTURE RESEARCH, 1979, 69 (02): : 180 - 190
  • [10] SIMPLE AND EFFICIENT GENERATION OF MARKED CLONES IN DROSOPHILA
    HARRISON, DA
    PERRIMON, N
    [J]. CURRENT BIOLOGY, 1993, 3 (07) : 424 - 433