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PARL paves the way to apoptosis

Naotada Ishihara1, Katsuyoshi Mihara2

  • 1Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.

Nature Cell Biology
|April 1, 2017
PubMed

Insights

The mitochondrial rhomboid peptidase PARL processes the pro-apoptotic protein Smac/DIABLO, enabling its release to trigger apoptosis by inhibiting XIAP. This clarifies PARL's role in programmed cell death signaling.

Area of Science:

  • Mitochondrial biology
  • Cell death pathways
  • Protease function

Background:

  • The mitochondrial inner membrane rhomboid peptidase PARL (Presenilin-associated rhomboid-like protein) is implicated in cellular signaling.
  • PARL's specific role in the programmed cell death (apoptosis) pathway has not been fully elucidated.
  • Understanding PARL's function is crucial for deciphering mitochondrial regulation of cell fate.

Purpose of the Study:

  • To investigate the role of PARL in apoptosis.
  • To determine if PARL processes known pro-apoptotic factors.
  • To elucidate the mechanism by which PARL influences cell death.

Main Methods:

  • Biochemical assays to assess protein processing.
  • Cellular studies to monitor apoptosis induction.
  • Western blotting to detect protein cleavage and localization.

Main Results:

  • PARL directly processes the mitochondrial pro-apoptotic protein Smac (also known as DIABLO).
  • This processing event facilitates the release of Smac/DIABLO from mitochondria to the cytosol.
  • Released Smac/DIABLO antagonizes Inhibitor of Apoptosis Proteins (IAPs), specifically XIAP, thereby promoting caspase activation and apoptosis.

Conclusions:

  • PARL acts as a key regulator of apoptosis by processing Smac/DIABLO.
  • The proteolytic activity of PARL on Smac/DIABLO is essential for its release and subsequent apoptotic function.
  • This finding establishes a direct link between PARL activity and the execution phase of apoptosis.

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