Research Highlight

New insights into mitochondrial structure during cell death.

The crista junction architecture in neurons. (A) A tomographic slice from the volume of a CNS mitochondrion found near a synapse in the striatum. The arrowhead points to a crista junction opening. Synaptic mitochondria in the CNS are typically small with mostly lamellar cristae. Even with lamellar cristae, the narrow, tubular crista junction architecture prevails in brain mitochondria and the opening is at the end and not on the side of the cristae. Scale = 100 nm. (B) A tomographic slice from the volume of a PNS mitochondrion found in the axon of a spinal root. The crista junction is boxed and expanded 4x in the insert at left (arrowhead). PNS axonal mitochondria are typically elongated with longitudinally oriented cristae and often show a condensed matrix as seen here. Even with structural features different from CNS mitochondria, PNS axonal mitochondria nevertheless have the same crista junction architecture and again, the opening is at the end and not on the side of the cristae. Scale = 400 nm. (C) Cut-away model of neuronal mitochondria. Tubular cristae (low asterisk) can be oriented in different directions and have different diameters in CNS mitochondria, but are typically longitudinal in PNS mitochondria and the crista junction is at the end of the tube (arrow). The crista junction is relatively uniform in size, even for lamellar cristae (arrowheads). Mitochondria have 3 membrane systems, the outer membrane (OM), inner boundary (IBM), and cristae, and 3 compartments, the matrix, intermembrane space (IM), and intracristal space (IC). The outer membrane was made translucent to better visualize the crista junctions.

December 2009 — In this research effort, NCMIR neuroscientists and investigators at the Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, examined the pivotal role mitochondria play in the cascade of events associated with cell death pathways involved with several forms of neurodegeneration. NCMIR’s ability to successfully slice through an electron tomographic volume to image fragmented mitochondria revealed cristae vesiculation, cristae degradation and swollen endoplasmic reticulum.

This study confirmed 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. There is remaining 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.

In this paper NCMIR scientists thoroughly 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.

Full text: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19464290

Related Publications

G. Perkins, E. Bossy-Wetzel, M.H. Ellisman, New insights into mitochondrial structure during cell death, Exp Neurol 218 (2009)  183-192.