New insights into mitochondrial structure during cell death.
Mitochondria play a pivotal role in the cascade of events associated with cell death pathways that are involved with several forms of neurodegeneration. Recent findings show that in the Bax/Bak-dependent pathway of apoptosis, the release of cytochrome c from mitochondria is a consequence of two carefully coordinated events: opening of crista junctions triggered by OPA1 oligomer disassembly and formation of outer membrane pores. Both steps are necessary for the complete release of pro-apoptotic proteins. The remodeling of mitochondrial structure accompanies this pathway, including mitochondrial fission, and cristae and crista junction alterations. Yet, there is controversy surrounding the timing of certain remodeling events and whether they are necessary early events required for the release of pro-apoptotic factors or are simply a downstream after-effect. Here, we analyze the current knowledge of mitochondrial remodeling during cell death and discuss what structural alterations occur to this organelle during neurodegeneration, focusing on the higher resolution structural correlates obtained by electron microscopy and electron tomography.
Perkins
Guy
G
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, 92093-0608, USA. perkins@ncmir.ucsd.edu
Bossy-Wetzel
Ella
E
Ellisman
Mark H
MH
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D055032:Electron Microscope Tomography; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D009410:Nerve Degeneration / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human