Mitotic ER-mitochondria contact enhances mitochondrial Ca2+ influx to promote cell division

Abstract

Cell division is tightly regulated and requires an expanded energy supply. However, how this energy is generated remains unclear. Here, we establish a correlation between two mitochondrial Ca²⁺ influx events and ATP production during mitosis. While both events promote ATP production during mitosis, the second event, the Ca²⁺ influx surge, is substantial. To facilitate this Ca²⁺ influx surge, the lamin B receptor (LBR) organizes a mitosis-specific endoplasmic reticulum (ER)-mitochondrial contact site (ERMCS), creating a rapid Ca²⁺ transport pathway. LBR acts as a tether, connecting the ER Ca²⁺ release channel IP₃R with the mitochondrial VDAC2. Depletion of LBR disrupts the Ca²⁺ influx surge, reduces ATP production, and postpones the metaphase-anaphase transition and subsequent cell division. These findings provide insight into the mechanisms underlying mitotic energy production and supply required for cell proliferation.

Keywords: CP: Cell biology; CP: Metabolism; Ca(2+); ER-mitochondrial contact; LBR; VDAC2; cell cycle; cell division; energy generation; metaphase-anaphase transition; mitochondria; mitosis.