The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice

TLDR

The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. The authors generated complete and tissue‑specific Drp1 knockout mice to investigate its in vivo role. Loss of Drp1 causes embryonic lethality by E11.5, widespread mitochondrial and peroxisomal network formation, cerebellar defects with giant mitochondria, impaired developmental apoptosis, and underscores the essential role of Drp1‑mediated organelle division in mouse development.

Abstract

The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice.