Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster

Ying-Chen Claire Hou1, Suganthi Chittaranjan, Sharon González Barbosa

  • 1The Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada.

The Journal of Cell Biology
|September 17, 2008
PubMed

Insights

This study reveals that cell death genes and signaling pathways regulate autophagy in Drosophila. Autophagy partially contributes to cell death during oogenesis, highlighting coordinated regulation of cell death and autophagy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The interplay between autophagy and apoptosis is complex and not fully understood.
  • Regulatory mechanisms governing the interaction between these two cell death pathways remain largely unknown.

Purpose of the Study:

  • To systematically investigate the role of cell death-related genes in regulating starvation-induced autophagy in Drosophila melanogaster.
  • To elucidate the molecular mechanisms coordinating autophagic and apoptotic processes in vivo.

Main Methods:

  • Systematic screening of Drosophila melanogaster cell death-related genes.
  • Analysis of gene function in cultured D. melanogaster cells and during oogenesis.
  • Investigating the impact of mutations in autophagy-related genes (Atg1, Atg7) on cell death markers.

Main Results:

  • Six cell death genes (Dcp-1, hid, Bruce, Buffy, debcl, p53) and Ras-Raf-MAPK pathway components regulate autophagy in D. melanogaster cells.
  • Autophagy is induced at specific nutrient-dependent checkpoints during oogenesis (germarium and mid-oogenesis).
  • The effector caspase Dcp-1 and inhibitor of apoptosis protein Bruce regulate both autophagy and starvation-induced cell death during oogenesis.
  • Mutations in Atg1 and Atg7 partially reduced DNA fragmentation in degenerating egg chambers, suggesting autophagy's role in ovarian cell death.

Conclusions:

  • Cell death genes and signaling pathways are critical regulators of autophagy in Drosophila.
  • Autophagy plays a partial role in ovarian cell death during oogenesis.
  • This study provides novel insights into the coordinated regulation of autophagy and apoptosis in vivo.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...