Is mPTP the gatekeeper for necrosis, apoptosis, or both?

Kathleen W. Kinnally, Pablo M. Peixoto, Shin Young Ryu, Laurent M. Dejean

Research output: Contribution to journalReview articlepeer-review

Abstract

Permeabilization of the mitochondrial membranes is a crucial step in apoptosis and necrosis. This phenomenon allows the release of mitochondrial death factors, which trigger or facilitate different signaling cascades ultimately causing the execution of the cell. The mitochondrial permeability transition pore (mPTP) has long been known as one of the main regulators of mitochondria during cell death. mPTP opening can lead to matrix swelling, subsequent rupture of the outer membrane, and a nonspecific release of intermembrane space proteins into the cytosol. While mPTP was purportedly associated with early apoptosis, recent observations suggest that mitochondrial permeabilization mediated by mPTP is generally more closely linked to events of late apoptosis and necrosis. Mechanisms of mitochondrial membrane permeabilization during cell death, involving three different mitochondrial channels, have been postulated. These include the mPTP in the inner membrane, and the mitochondrial apoptosis-induced channel (MAC) and voltage-dependent anion-selective channel (VDAC) in the outer membrane. New developments on mPTP structure and function, and the involvement of mPTP, MAC, and VDAC in permeabilization of mitochondrial membranes during cell death are explored. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1813
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Bcl-2 family proteins
  • MAC, mitochondrial apoptosis-induced channel
  • MPTP, mitochondrial permeability transition pore
  • Patch clamp
  • Pharmacology
  • VDAC, voltage-dependent anion-selective channel

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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