PUBLICATION

A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development

Authors
Lu, G., Ren, S., Korge, P., Choi, J., Dong, Y., Weiss, J., Koehler, C., Chen, J.N, and Wang, Y.
ID
ZDB-PUB-070330-30
Date
2007
Source
Genes & Development   21(7): 784-796 (Journal)
Registered Authors
Chen, Jau-Nian, Choi, Jayoung, Koehler, Carla
Keywords
Mitochondrial permeability transition pore, protein phosphatase, cell death, heart failure, developmental defects, zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Brain/embryology
  • Brain/metabolism
  • Cell Membrane Permeability
  • Cell Survival
  • Embryo, Nonmammalian/enzymology
  • Embryo, Nonmammalian/metabolism
  • Heart/embryology
  • Humans
  • Mice
  • Mitochondria/enzymology*
  • Mitochondria/metabolism
  • Mitochondrial Membrane Transport Proteins/metabolism*
  • Molecular Sequence Data
  • Myocytes, Cardiac/metabolism
  • Phosphoprotein Phosphatases/genetics
  • Phosphoprotein Phosphatases/metabolism
  • Phosphoprotein Phosphatases/physiology*
  • Sequence Alignment
  • Zebrafish/embryology*
  • Zebrafish/metabolism
PubMed
17374715 Full text @ Genes & Dev.
Abstract
Mitochondria play a central role in the regulation of programmed cell death signaling. Here, we report the finding of a mitochondrial matrix-targeted protein phosphatase 2C family member (PP2Cm) that regulates mitochondrial membrane permeability transition pore (MPTP) opening and is essential for cell survival, embryonic development, and cardiac function. PP2Cm is highly conserved among vertebrates, with the highest expression levels detected in the heart and brain. Small hairpin RNA (shRNA)-mediated knockdown of PP2Cm resulted in cell death associated with loss of mitochondrial membrane potential in cultured cardiac mycoytes and an induction of hepatocyte apoptosis in vivo. PP2Cm-deficient mitochondria showed elevated susceptibility to calcium-induced MPTP opening, whereas mitochondrial oxidative phosphorylation activities were not affected. Finally, inactivation of PP2Cm in developing zebrafish embryos caused abnormal cardiac and neural development as well as heart failure associated with induced apoptosis. These data suggest that PP2Cm is a novel mitochondrial protein phosphatase that has a critical function in cell death and survival, and may play a role in regulating the MPTP opening.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes