C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through...

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Externalization of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane is a hallmark of apoptosis in mammals.
• The molecular mechanisms activating and mediating PS externalization in apoptotic cells remain largely unknown.

Purpose of the Study:

• To investigate the conserved mechanisms of phosphatidylserine externalization during apoptosis in Caenorhabditis elegans.
• To identify the factors involved in regulating PS exposure on apoptotic cells and their role in cell-corpse engulfment.

Main Methods:

• Development of an annexin V-based phosphatidylserine labeling method for live cell imaging.
• Genetic inactivation of WAH-1 (AIF homologue) and SCRM-1 (phospholipid scramblase) in C. elegans.
• In vitro biochemical assays to assess WAH-1 and SCRM-1 interaction and enzymatic activity.

Main Results:

• A majority of apoptotic germ cells in C. elegans exhibit surface-exposed phosphatidylserine, confirming conserved PS externalization.
• Inactivation of WAH-1 or SCRM-1 significantly reduced PS exposure on apoptotic germ cells and impaired cell-corpse engulfment.
• WAH-1 directly associates with SCRM-1 and activates its phospholipid scrambling activity in vitro.

Conclusions:

• The C. elegans apoptosis-inducing factor homologue WAH-1, upon release from mitochondria, promotes plasma membrane PS externalization.
• WAH-1 acts through its downstream effector, SCRM-1, to mediate PS externalization, a conserved event in apoptosis.
• This WAH-1-SCRM-1 pathway is crucial for efficient cell-corpse engulfment in C. elegans.