A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

Cell Death Differ. 2007 Jul;14(7):1275-84. doi: 10.1038/sj.cdd.4402145. Epub 2007 Apr 20.

Abstract

Mitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release is accompanied by fragmentation of the mitochondrial reticulum and by remodelling of the internal structure of the organelle. Here we review data supporting the existence of a regulatory network in the inner mitochondrial membrane that includes optic atrophy 1 (Opa1), a dynamin-related protein, and presenilin-associated rhomboid-like (Parl), a rhomboid protease. Opa1 regulates remodelling of the cristae independent of its effect on fusion. Cristae remodelling conversely requires Parl, which participates in the production of a soluble form of Opa1 retrieved together with the integral membrane one in oligomers that are disrupted early during apoptosis. Parl itself is regulated by proteolysis to generate a cleaved form, which in turn modulates the shape of the mitochondrial reticulum. Cleavage of Parl depends on its phosphorylation state around the cleavage site, implicating mitochondrial kinases and phosphatases in the regulation of mitochondrial shape.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Shape / physiology
  • Evolution, Molecular
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Humans
  • Metalloproteases / genetics
  • Metalloproteases / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Peptide Hydrolases / metabolism
  • Phosphorylation

Substances

  • Mitochondrial Proteins
  • Metalloproteases
  • Peptide Hydrolases
  • PARL protein, human
  • GTP Phosphohydrolases
  • OPA1 protein, human