TY - JOUR
T1 - Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division
AU - Adachi, Yoshihiro
AU - Itoh, Kie
AU - Yamada, Tatsuya
AU - Cerveny, Kara L.
AU - Suzuki, Takamichi L.
AU - Macdonald, Patrick
AU - Frohman, Michael A.
AU - Ramachandran, Rajesh
AU - Iijima, Miho
AU - Sesaki, Hiromi
N1 - Funding Information:
We thank members of the M.I. and H.S. labs for helpful discussion. This work was supported by grants to M.I. (NIH, GM084015), H.S. (NIH, GM089853 and NS084154; AHA, 15GRNT25380005), and M.A.F. (NIH, GM084251).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.
AB - Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.
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U2 - 10.1016/j.molcel.2016.08.013
DO - 10.1016/j.molcel.2016.08.013
M3 - Article
C2 - 27635761
AN - SCOPUS:84991721053
SN - 1097-2765
VL - 63
SP - 1034
EP - 1043
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -