Open AccessDepletion of phosphatidylinositol 4-phosphate at the Golgi translocates K-Ras to mitochondria
Author(s) -
Taylor E. Miller,
Karen M. Henkels,
Mary Huddleston,
Richard L. Salisbury,
Saber M. Hussain,
Atsuo T. Sasaki,
Kwang-Jin Cho
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.231886
Subject(s) - biology , golgi apparatus , microbiology and biotechnology , phosphatidylinositol , gtpase , mitochondrion , small gtpase , protein subunit , kinase , signal transduction , biochemistry , endoplasmic reticulum , gene
Ras proteins are small GTPases localized to the plasma membrane (PM), which regulate cellular proliferation, apoptosis and differentiation. After a series of posttranslational modifications, H- and N-Ras traffic to the PM from the Golgi via the classical exocytic pathway, but the exact mechanism of K-Ras trafficking to the PM from the ER is not fully characterized. ATP5G1 is one of the three proteins that compose subunit c of the F0 complex of the mitochondrial ATP synthase. In this study, we show that overexpression of the mitochondrial targeting sequence of ATP5G1 perturbs glucose metabolism, inhibits oncogenic K-Ras signaling, and redistributes phosphatidylserine (PtdSer) to mitochondria and other endomembranes, resulting in K-Ras translocation to mitochondria. Also, it depletes phosphatidylinositol (PI) 4-phosphate (P) at the Golgi. Glucose supplementation restores PtdSer and K-Ras PM localization and PI4P at the Golgi. We further show that inhibition of the Golgi-localized PI4-kinases (PI4Ks) translocates K-Ras, and PtdSer to mitochondria and endomembranes, respectively. We conclude that PI4P at the Golgi regulates the PM localization of PtdSer and K-Ras.