Mitochondria are essential organelles regulating a myriad of cellular processes ranging from cell death to various signaling pathways. Vital to mitochondrial functions is their ability to modulate their shape via two opposing processes: fusion and fission. Fission, characterized by the division of one mitochondrion in two daughter mitochondria, is a complex process involving the participation of multiple organelles such as the endoplasmic reticulum (ER) and lysosomes. In this manuscript, research fellow Maxime Boutry in the laboratory of Peter K. Kim provide evidence that the ER and lysosomes act in concert during the mitochondrial division process. Super resolution live fluorescent imaging showed that the ER recruits lysosomes to the mitochondrial division site via the formation of three-way contact between the three organelles. This involves the interaction between the small GTPase Rab7, the lipid transfer protein ORP1L and the ER resident VAPs proteins. At the mitochondrial division site, ORP1L mediates a Phosphatidylinositol-4-phosphate (PI(4)P) signaling, likely by transferring PI(4)P from lysosome to the mitochondrial division site, contributing to the completion of mitochondrial membranes scission. This work implicates that the various organelles participating in mitochondrial division act in cooperation and suggest that the small phospholipid PI(4)P is a key player of the division process.

Click here to read more: ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division