Interaction between PI3K and the VDAC2 channel tethers Ras-PI3K-positive endosomes to mitochondria and promotes endosome maturation

Aya O. Satoh; Yoichiro Fujioka; Sayaka Kashiwagi; Aiko Yoshida; Mari Fujioka; Hitoshi Sasajima; Asuka Nanbo; Maho Amano; Yusuke Ohba

Cell Reports (Mar 2023)

Interaction between PI3K and the VDAC2 channel tethers Ras-PI3K-positive endosomes to mitochondria and promotes endosome maturation

Aya O. Satoh,
Yoichiro Fujioka,
Sayaka Kashiwagi,
Aiko Yoshida,
Mari Fujioka,
Hitoshi Sasajima,
Asuka Nanbo,
Maho Amano,
Yusuke Ohba

Affiliations

Aya O. Satoh: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Yoichiro Fujioka: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Sayaka Kashiwagi: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Aiko Yoshida: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Mari Fujioka: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Hitoshi Sasajima: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan
Asuka Nanbo: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan
Maho Amano: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan
Yusuke Ohba: Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Kita-ku, Sapporo 060-8638, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Kita-ku, Sapporo 060-8638, Japan; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112229

Abstract

Read online

Summary: Intracellular organelles of mammalian cells communicate with one another during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identify voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 tethers endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and promotes clathrin-independent endocytosis, as well as endosome maturation at membrane association sites. With an optogenetics system to induce mitochondrion-endosome association, we find that, in addition to its structural role in such association, VDAC2 is functionally implicated in the promotion of endosome maturation. The mitochondrion-endosome association thus plays a role in the regulation of clathrin-independent endocytosis and endosome maturation.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords