Mitochondria continually change their shape in response to different cellular stimuli. For example, mitochondrial fragmentation is seen during apoptosis in mammalian cells while mitochondrial fusion is observed during cell-cell fusion induced by polyethylene glycol or during mating in yeast. Although some proteins that participate in mitochondrial fusion/division have been identified, the mechanisms are still not known. MGM-1 is a dynamin-related protein, which is localized to the intermembrane space where it is bound to the inner membrane. Yeast mutant and interference with MGM-1 function in mammalian cells by expression of dominant negative mutant of MGM-1 or by siRNA causes mitochondria to fragment. Here we show that
eat-3(
ad426) has a mutation in C. elegans
mgm-1 gene (D2013.5), changing a valine to isoleucine in the GTPase. This mutation causes mitochondria to fragment. Mitochondrial fragmentation is reversed by expression of wild type MGM-1 under control of the
myo-3 promoter. The
eat-3 mutant is characterized by sluggishness and slow growth similar to N2 worms fed bacteria expressing double strand RNA or injected with double strand
mgm-1 RNA. To further investigate how mitochondria are affected, we performed ultrastructural analysis of
eat-3 worms. The
eat-3 mitochondria had abnormal inner membrane septae and electron dense inclusions. The inner membrane septae suggest inner membrane division without outer membrane division. Similarly, worms expressing temperature sensitive mutant MGM-1 when incubated at a non-permissive temperature showed mitochondrial fragmentation was monitored. These results indicate that mitochondrial fragmentation induced by MGM-1 mutant is due to mitochondrial division. FZO-1 (encoded by ZK1248.14), a homologue of fuzzy onion in D. melanogaster, mitofusin in mammal or FZO1 in budding yeast, is an outer membrane protein involved in mitochondrial fusion. Although FZO-1 knockdown induces mitochondrial fragmentation as well, worms are not as sluggish as MGM-1 knockdown or
eat-3 , suggesting that MGM-1 has additional functions within cristae.