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Interaction Between Phosphoinositide 3-Kinase and the VDAC2 Channel Tethers Endosomes to Mitochondria and Promotes Endosome Maturation

47 Pages Posted: 26 Jan 2021 Publication Status: Review Complete

See all articles by Aya O. Satoh

Aya O. Satoh

Hokkaido University - Department of Cell Physiology

Yoichiro Fujioka

Hokkaido University - Department of Cell Physiology

Sayaka Kashiwagi

Hokkaido University - Department of Cell Physiology

Aiko Yoshida

Hokkaido University - Department of Cell Physiology

Mari Fujioka

Hokkaido University - Department of Cell Physiology

Hitoshi Sasajima

Hokkaido University - Department of Cell Physiology

Asuka Nanbo

Hokkaido University - Department of Cell Physiology

Maho Amano

Hokkaido University - Department of Cell Physiology

Yusuke Ohba

Hokkaido University - Department of Cell Physiology

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Abstract

Intracellular organelles of mammalian cells communicate with each other during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identified 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 was found to tether endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and to promote clathrin-independent endocytosis as well as endosome maturation at membrane contact sites. With a newly developed optogenetics system to induce mitochondrion-endosome association, we found that, in addition to its structural role in such association, the pore function of VDAC2 is also required for the promotion of endosome maturation. Our findings thus uncover a previously unappreciated role of mitochondrion-endosome association in the regulation of endocytosis and endosome maturation.

Keywords: voltage-dependent anion channel 2 (VDAC2), phosphoinositide 3-kinase (PI3K), endocytosis, endosomes, mitochondria, interorganelle association, membrane contact site, optogenetics, imaging

Suggested Citation

Satoh, Aya O. and Fujioka, Yoichiro and Kashiwagi, Sayaka and Yoshida, Aiko and Fujioka, Mari and Sasajima, Hitoshi and Nanbo, Asuka and Amano, Maho and Ohba, Yusuke, Interaction Between Phosphoinositide 3-Kinase and the VDAC2 Channel Tethers Endosomes to Mitochondria and Promotes Endosome Maturation. Available at SSRN: https://ssrn.com/abstract=3773811 or http://dx.doi.org/10.2139/ssrn.3773811
This version of the paper has not been formally peer reviewed.

Aya O. Satoh

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Yoichiro Fujioka

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Sayaka Kashiwagi

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Aiko Yoshida

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Mari Fujioka

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Hitoshi Sasajima

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Asuka Nanbo

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Maho Amano

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

Yusuke Ohba (Contact Author)

Hokkaido University - Department of Cell Physiology ( email )

Sapporo
Japan

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