Mitochondrial E3 ubiquitin ligase MARCH5 is required for mouse oocyte meiotic maturation†

Knockdown of MARCH5 blocks mouse oocyte maturation at MI stage with the continuous activation of the spindle assembly checkpoint (SAC) and the failure of Cyclin B1 degradation, perhaps through inducing mitochondrial dysfunctions. As the most abundant organelles in oocytes, mitochondria play an important role in maintaining oocyte quality. Here, we report that March5, encoding a mitochondrial ubiquitin ligase that promotes mitochondrial elongation, plays a critical role in mouse oocyte meiotic maturation via regulating mitochondrial function. The subcellular localization of MARCH5 was similar to the mitochondrial distribution during mouse oocyte meiotic progression. Knockdown of March5 caused decreased ratios of the first polar body extrusion. March5-siRNA injection resulted in oocyte mitochondrial dysfunctions, manifested by increased reactive oxygen species, decreased ATP content as well as decreased mitochondrial membrane potential, leading to reduced ability of spindle formation and an increased ratio of kinetochore-microtubule detachment. Further study showed that the continuous activation of the spindle assembly checkpoint and the failure of Cyclin B1 degradation caused MI arrest and first polar body (PB1) extrusion failure in March5 knockdown oocytes. Taken together, our results demonstrated that March5 plays an essential role in mouse oocyte meiotic maturation, possibly via regulation of mitochondrial function and/or ubiquitination of microtubule dynamics- or cell cycle-regulating proteins.

Automated summary

Knockdown of MARCH5 in mouse oocytes leads to the arrest of oocyte maturation at the MI stage, characterized by the continuous activation of the spindle assembly checkpoint (SAC) and the failure of Cyclin B1 degradation. This may be due to the induction of mitochondrial dysfunctions by MARCH5 knockdown. MARCH5, a mitochondrial ubiquitin ligase that promotes mitochondrial elongation, is involved in regulating mitochondrial function during mouse oocyte meiotic maturation.