Mitochondrial Calcium uniporters are essential for meiotic progression in mouse oocytes by controlling Ca2+ entry

Objectives The alteration of bioenergetics by oocytes in response to the demands of various biological processes plays a critical role in maintaining normal cellular physiology. However, little is known about the association between energy sensing and energy production with energy‐dependent cellular processes like meiosis. Materials and methods We demonstrated that cell cycle‐dependent mitochondrial Ca2+ connects energy sensing to mitochondrial activity in meiosis progression within mouse oocytes. Further, we established a model in mouse oocytes using siRNA knockdowns that target mitochondrial calcium uniporters (MCUs) in order to inhibit mitochondrial Ca2+ concentrations. Results Decreased numbers of oocytes successfully progressed to the germinal vesicle stage and extruded the first polar body during in vitro culture after inhibition, while spindle checkpoint‐dependent meiosis was also delayed. Mitochondrial Ca2+ levels changed, and this was followed by altered mitochondrial masses and ATP levels within oocytes during the entirety of meiosis progression. Abnormal mitochondrial Ca2+ concentrations in oocytes then hindered meiotic progress and activated AMP‐activated protein kinase (AMPK) signalling that is associated with gene expression. Conclusions These data provide new insight into the protective role that MCU‐dependent mitochondrial Ca2+ signalling plays in meiotic progress, in addition to demonstrating a new mechanism of mitochondrial energy regulation by AMPK signalling that influences meiotic maturation.
When KD‐MCU occurs in oocytes due to impaired mitochondrial function, cytosolic ATP levels decline. The energy sensor AMPK is activated and phosphorylated in response to the increased energetic stress. Excessive activation of AMPK results in adverse effects on the resumption of meiosis. In addition, microtubule dynamics and tension establishment cannot efficiently be achieved, leading to decreased meiotic progression. These observations all implicate MCU as being critical for meiotic progression.