Research ArticleINTERORGANELLE SIGNALING

Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2

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Science Signaling  07 May 2019:
Vol. 12, Issue 580, eaat7397
DOI: 10.1126/scisignal.aat7397

PC2 separates mitochondria from the ER

Patients with loss-of-function mutations in polycystin (PC) 1 or 2 develop fluid-filled cysts due to excessive proliferation of kidney epithelial cells. Kuo et al. found that loss of the ER cation channel PC2 led to increased abundance of the mitochondrial fusion factor MFN2 and enhanced tethering of mitochondria to the ER. The increased mitochondria-ER association resulted in greater mitochondrial Ca2+ influx, biogenesis, and respiration and cellular proliferation, which in cultured cells and mouse models of polycystic kidney disease was rescued by deficiency in MFN2. These results show that PC2 acts to restrict mitochondrial tethering to the ER in kidney cells to prevent inappropriate Ca2+-dependent increases in mitochondrial function and cellular proliferation.

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