View Program - 63rd Annual Drosophila Research Conference

Mitochondria, the bioenergetics powerhouses and biosynthetic centers of the cell, are also implicated in many important cellular processes, such as cell death, autophagy, aging, and regulation of immune response and inflammation. Although stereotypically drawn as static organelles, mitochondria are in fact constantly changing shape and subcellular distribution according to function, energy and metabolic demands of the cell. Mitochondrial shapes usually range from small spheres and short tubules to elongated tubules and reticular networks, and these changes are mainly controlled by the balance between two opposing mechanisms of membrane dynamics, fusion and fission (fragmentation). Proper membrane dynamics is essential for maintenance and function of the mitochondria, whereas abrogation of this balance can lead to common diseases, including several neurodegenerative diseases and cancer. The first gene involved in mitochondrial dynamics, fuzzy onions (fzo), was discovered by Hales and Fuller in 1997 as a mediator of the fusion of the entire Drosophila spermatid mitochondria into a giant sphere called Nebenkern. Consequently, orthologs of Fzo, termed mitofusins, have been discovered in organisms from yeast to human, belonging to the dynamin-related protein superfamily of large GTPases. Mitofusins are expressed on the outer mitochondrial membrane (OMM), tethering together adjacent mitochondria by promoting mitochondrial docking through their auto-oligomerization in trans.

In Drosophila spermatids, individual mitochondria aggregate near the newly formed haploid nucleus and subsequently coalesce and fuse into a Nebenkern. The Nebenkern is composed of two giant mitochondria wrapped around each other and arranged in an onion-like structure of layers upon layers of mitochondrial membranes. Although detailed ultrastructural description of Nebenkern formation was already reported five decades ago, the molecular mechanisms underlying the formation of this extraordinary organelle remains largely obscure. Furthermore, it remained unknown whether Fzo has been evolved to uniquely promote fusion of the mitochondria into a giant sphere rather than to reticular network, as well as to what extent the canonical fusion machinery might be involved in Nebenkern formation. Here, I will present our recent studies aiming to address these and related questions, presenting our ongoing unpublished work on the molecular and anatomical mechanisms underlying Nebenkern formation.

Robustness of the canonical mitochondrial fusion machinery promotes Nebenkern formation in Drosophila spermatids