Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging.

Abstract

Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1 supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1), Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.