CMT 2A implications in Molecular mechanism of mitochondrial membrane fusion

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Biochim Biophys Acta. 2006 Mar 9

Molecular mechanism of mitochondrial membrane fusion.

EE, Detmer SA, Chan DC.

Division of Biology, California Institute of Technology, 1200 East

California Blvd., MC114-96, Pasadena, CA 91125, USA.

Mitochondrial fusion requires coordinated fusion of the outer and

inner membranes. This process leads to exchange of contents, controls

the shape of mitochondria, and is important for mitochondrial

function. Two types of mitochondrial GTPases are essential for

mitochondrial fusion. On the outer membrane, the fuzzy

onions/mitofusin proteins form complexes in trans that mediate

homotypic physical interactions between adjacent mitochondria and are

likely directly involved in outer membrane fusion. Associated with

the inner membrane, the OPA1 dynamin-family GTPase maintains membrane

structure and is a good candidate for mediating inner membrane

fusion. In yeast, Ugo1p binds to both of these GTPases to form a

fusion complex, although a related protein has yet to be found in

mammals. An understanding of the molecular mechanism of fusion may

have implications for Charcot-Marie-Tooth subtype 2A and autosomal

dominant optic atrophy, neurodegenerative diseases caused by

mutations in Mfn2 and OPA1.