Published online
doi:10.1083/jcb.1764iti3
The Journal of Cell Biology, Vol. 176, No. 4, 373a-
The Rockefeller University Press, 0021-9525 $30.00
© LeBrasseur
Pro-diversity mitofusins
Affirmative action groups would be proud of Mfn proteins. These fusion proteins work better with diverse partners, say Detmer and Chan (page 405). The results might help explain why only certain neurons are susceptible in Charcot-Marie-Tooth disease 2A (CMT2A).
CMT2A is a neurodegenerative disease caused by dominant mutations in the mammalian mitofusin Mfn2. Along with Mfn1, Mfn2 forms oligomers that tether the outer membranes of mitochondria before they fuse. The loss of either Mfn1 or Mfn2 causes some mitochondrial fragmentation by impairing fusion.
The authors now show that, alone, many Mfn2 mutants associated with CMT2A cannot fuse mitochondria. The mutants formed complexes with either Mfn1 or wild-type Mfn2, but only complexes that included Mfn1 fused mitochondria. Mitochondria with only Mfn1 fused with mitochondria with only mutant Mfn2, suggesting that the heterooligomers do not need to form on the same organelle.
The group suggests that the neurons that die in patients with CMT2A, including long motor and sensory neurons, might have particularly low ratios of Mfn1 to Mfn2. They would thus lack enough Mfn1 to form productive complexes with the mutant Mfn2. The group now needs to determine how heterooligomers work and their importance compared to homooligomers. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations
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J. Cell Biol. 2007 176: 405-414.
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