Robustness of the Canonical Mitochondrial Fusion Machinery Promotes Nebenkern Formation in Drosophila Spermatids

Mitochondria are the bioenergetics powerhouses and biosynthetic centers of the cell, and are implicated in many important cellular processes. The mitochondria are constantly changing shape and subcellular distribution according to function, energy and metabolic demands of the cell. Mitochondrial morphology usually ranges from small spheres and short tubules to elongated tubules and reticular networks. These changes are mainly controlled by the balance between two opposing mechanisms of membrane dynamics, fusion and fission, which when perturbed, can lead to common diseases, including several neurodegenerative diseases and cancer.

Perhaps the most dramatic morphological changes and structural organizations of the mitochondria occur during spermatogenesis. In Drosophila spermatids, individual mitochondria aggregate near the newly formed haploid nucleus and subsequently coalesce and fuse into a giant sphere called Nebenkern. The Nebenkern is composed of two giant mitochondria wrapped around each other and arranged in an onion-like spherical segments of layers upon layers. During subsequent spermatid elongation stages, the Nebenkern is transformed from a 6.7 µm sphere to two, 1.8 mm long, cylindrical mitochondrial derivatives extending alongside the axoneme. 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.