Kinase

Cell division

Cell biology

Biology

Cytosol

Uniporter

Biochemistry

Protein kinase A

Phosphorylation

Spindle apparatus

Mitosis

AMPK

Enzyme

Mitotic exit

Mitochondrion

Cell

Nature Cell Biology

The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis. Inhibition of mitochondrial Ca2+ transients via MCU depletion causes spindle checkpoint-dependent mitotic delay. Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). Our results establish a critical role for AMPK- and MCU-dependent mitochondrial Ca2+ signalling in mitosis and reveal a mechanism of mitochondrial metabolic adaptation to acute cellular energy stress. Zhao et al. find that AMPK phosphorylates and activates the mitochondrial Ca2+ uniporter in response to low energy status in mitosis, allowing Ca2+ entry into mitochondria to boost mitochondrial respiration.

AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression