Fuzzy Onions and the Nebenkern

The Nebenkern is a remarkable mitochondrial formation in the sperm of insects such as Drosophila. Just after meiosis is completed, the mitochondria of the spermatid collect on one side of the haploid pronucleus and fuse together into two giant aggregates. These aggregated mitochondria then wrap around one another to produce the spherical Nebenkern. When viewed in cross-section under the transmission electron microscope, the Nebenkern resembles an onion slice, and this early stage of spermatogenesis is called the "onion stage." When the flagellum elongates, the two mitochondrial regions of the Nebenkern unfold and elongate down the side of the axoneme (Figure 1; Tates 1971; Fuller 1993).

Figure 1
Figure 1   Diagram of Nebenkern formation in Drosophila. The leftmost diagram represents the aggregation of the mitochondria beneath the haploid sperm nucleus. The second diagram represents the "onion stage" where the aggregated mitochondria fuse into two "supermitochondria" and wrap around one another. The third diagram represents early elongation, while the rightmost diagram repesents a mid-elongation stage. (After Hales and Fuller 1997.)

Mitochondrial fusion is not unique to insect spermatids. Serial sections of rodent skeletal muscle, lymphocytes, liver, and spinal ganglial cells show evidence of fused mitochondria, and the mitochondria of the yeast S. cerevisiae may indeed be one large branched reticulum (see Literature Cited in Hales and Fuller 1997). Although many of these events are developmentally regulated, the mediators of mitochondrial fusion have not been identified.

The only known mediator of mitochondrial fusion is the one that regulates Nebenkern formation. It is the product of the fuzzy onions gene, and it appears to be a transmembrane GTPase that is associated with the mitochondria during the time of fusion (Hales and Fuller 1997). Male flies with mutations of the fuzzy onion are sterile. They have defective Nebenkern due to the fact that the mitochondria have failed to fuse into the two giant mitochondria. Rather, the unfused mitochondria wrap around each other and elongate. So the defect appears to be that of fusion, since the aggregation, wrapping, and elongation steps are all accomplished.

Figure 2
Figure 2   Cross-section through the Nebenkern of onion-stage spermatids. (A) The wild-type Nebenkern shows two compartments wrapped around one another. (B) The fuzzy onions Nebenkern shows unfused mitochondria. These individual mitochondria attempt to wrap around each other. (After Hales and Fuller 1997.)

Hales and Fuller (1997) isolated and sequenced the wild-type allele of fuzzy onions and demonstrated that the product of the wild-type gene was a GTPase with transmembrane domains. Mutations that altered the putative GTP binding site of the encoded enzyme inhibited the ability of the protein to mediate mitochondrial fusion. Using antibodies against the fuzzy onions GTPase, Hales and Fuller showed that this protein is associated with mitochondria during that narrow period of spermatogenesis corresponding to the time of mitochondrial fusion. It appears on the mitochodria just prior to fusion (during the last stages of meiosis II) and disappears soon afterward (after mitochondrial elongation).

The mechanism by which the fuzzy onions GTPase effects mitochondrial fusion is not known, nor is its mode of developmental regulation.

Literature Cited

Fuller, M. T. 1993. Spermatogenesis. In The Development of Drosophila. M. Bate and A. Martinez Arias (eds.) Cold Spring Harbor Press, Cold Spring Harbor, NY. pp. 71-147.

Hales, K. G. and Fuller, M. T. 1997. Developmentally regulated mitochondrial fusion mediated by a conserved novel predicted GTPase. Cell 90: 121-129.

Tates, A. D. 1971. Cytodifferentiation during Spermatogenesis in Drosophila melanogaster: An Electron Microscope Study. Rijksuniversiteit, Leiden.

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