In vivo functions of Drp1: lessons learned from yeast genetics and mouse knockouts

Abstract

Mitochondria grow, divide, and fuse in cells. Mitochondrial division is critical for the maintenance of the structure and function of mitochondria. Alterations in this process have been linked to many human diseases, including peripheral neuropathies and aging-related neurological disorders. In this review, we discuss recent progress in mitochondrial division by focusing on molecular and in vivo analyses of the evolutionarily conserved, central component of mitochondrial division, dynamin-related protein 1 (Drp1), in the yeast and mouse model organisms.

Keywords: Dynamin-related GTPase; Membrane fission; Mitochondrion; Mouse; Neurodegeneration; Yeast.

Figure 1. Mitochondrial morphology in yeast and mammalian cells

Mitochondria were visualized in yeast cells (wild-type and dnm1Δ), cultured mouse embryonic fibroblasts (MEFs) (wild-type and Drp1KO) and cultured Purkinje cells in vitro (wild-type and Drp1KO). Mitochondria were also examined in Purkinje cells and granule cells in vivo. Mitochondria formed short tubules in wild-type cells and net-like structures in yeast dnm1Δ cells. In Drp1KO MEFs, elongated mitochondrial tubules are highly connected. Upon addition of reactive oxygen species (50 μM H₂O₂) to the culture medium, elongated mitochondria became large spheres in Drp1KO MEFs. In Drp1KO Purkinje cells, mitochondria formed large spheres, which looked similar to those seen in H₂O₂-treated Drp1KO MEFs. When Drp1KO Purkinje cells were treated with antioxidants (1 mM N-acetylcysteine, NAC), mitochondria showed elongated tubules without forming spheres, which were similar to mitochondria in Drp1KO MEFs. These observations suggest that the loss of Drp1 induces oxidative damage in Drp1KO Purkinje cells and transforms elongated tubules into large spheres. In Drp1KO granule cells, mitochondria appeared normal. © Wakabayashi et al. (2009) and Kageyama et al. (2013).