Mitochondrial Swelling and Incipient Outer Membrane Rupture in Preapoptotic and Apoptotic Cells

• Grant number: 12/17525-6
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2012
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Antonio Sesso
• Grantee: Antonio Sesso
• Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

ABSTRACTOuter mitochondrial membrane (OMM) rupture was first noted inisolated mitochondria in which the inner mitochondrial membrane (IMM)had lost its selective permeability. This phenomenon referred to as mitochondrialpermeability transition (MPT) refers to a permeabilized innermembrane that originates a large swelling in the mitochondrial matrix,which distends the outer membrane until it ruptures. Here, we haveexpanded previous electron microscopic observations that in apoptoticcells, OMM rupture is not caused by a membrane stretching promoted bya markedly swollen matrix. It is shown that the widths of the rupturedregions of the OMM vary from 6 to 250 nm. Independent of the perforationsize, herniation of the mitochondrial matrix appeared to haveresulted in pushing the IMM through the perforation. A large, long focalherniation of the mitochondrial matrix, covered with the IMM, was associatedwith a rupture of the OMM that was as small as 6 nm. Contextually,the collapse of the selective permeability of the IMM may precede orfollow the release of the mitochondrial proteins of the intermembranespace into the cytoplasm. When the MPT is a late event, exit of the intermembranespace proteins to the cytoplasm is unimpeded and occursthrough channels that transverse the outer membrane, because so far,the inner membrane is impermeable. No channel within the outer membranecan expose to the cytoplasm a permeable inner membrane, becauseit would serve as a conduit for local herniation of the mitochondrial matrix.Anat Rec, 00:000-000, 2012. VC 2012 Wiley Periodicals, Inc.12345678910111213141516171819202122232425262728293031323334353637383940414243444546474849505152535455565758 (AU)