title: Topology of the mitochondrial inner membrane: dynamics and bioenergetic implications.
abstract: Electron tomography indicates that the mitochondrial inner membrane is not normally comprised of baffle-like folds as depicted in textbooks. In actuality, this membrane is pleomorphic, with narrow tubular regions connecting the internal compartments (cristae) to each other and to the membrane periphery. The membrane topologies observed in condensed (matrix contracted) and orthodox (matrix expanded) mitochondria cannot be interconverted by passive folding and unfolding. Instead, transitions between these morphological states likely involve membrane fusion and fission. Formation of tubular junctions in the inner membrane appears to be energetically favored, because they form spontaneously in yeast mitochondria following large-amplitude swelling and recontraction. However, aberrant, unattached, vesicular cristae are also observed in these mitochondria, suggesting that formation of cristae junctions depends on factors (such as the distribution of key proteins and/or lipids) that are disrupted during extreme swelling. Computer modeling studies using the "Virtual Cell" program suggest that the shape of the inner membrane can influence mitochondrial function. Simulations indicate that narrow cristae junctions restrict diffusion between intracristal and external compartments, causing depletion of ADP and decreased ATP output inside the cristae.
authors.affiliation: Resource for the Visualization of Biological Complexity, Division of Molecular Medicine, Wadsworth Center, Albany, New York 12201-0509, USA. carmen@wadsworth.org
authors.forename: C A
authors.initials: CA
authors.lastname: Mannella
authors.forename: D R
authors.initials: DR
authors.lastname: Pfeiffer
authors.forename: P C
authors.initials: PC
authors.lastname: Bradshaw
authors.forename: I I
authors.initials: II
authors.lastname: Moraru
authors.forename: B
authors.initials: B
authors.lastname: Slepchenko
authors.forename: L M
authors.initials: LM
authors.lastname: Loew
authors.forename: C E
authors.initials: CE
authors.lastname: Hsieh
authors.forename: K
authors.initials: K
authors.lastname: Buttle
authors.forename: M
authors.initials: M
authors.lastname: Marko
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure*; D008561:Membrane Fusion; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D008933:Mitochondrial Swelling; D014057:Tomography, X-Ray Computed