CMT 2A Pro-diversity mitofusins

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The Journal of Cell Biology, Vol. 176, No. 4, 373a-12 February 2007

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.