Porin Associates with Tom22 to Regulate the Mitochondrial Protein Gate Assembly

Haruka Sakaue; Takuya Shiota; Naoya Ishizaka; Shin Kawano; Yasushi Tamura; Kher Shing Tan; Kenichiro Imai; Chie Motono; Takatsugu Hirokawa; Kentaro Taki; Non Miyata; Osamu Kuge; Trevor Lithgow; Toshiya Endo

doi:10.1016/j.molcel.2019.01.003

Porin Associates with Tom22 to Regulate the Mitochondrial Protein Gate Assembly

Mol Cell. 2019 Mar 7;73(5):1044-1055.e8. doi: 10.1016/j.molcel.2019.01.003. Epub 2019 Feb 6.

Authors

Haruka Sakaue¹, Takuya Shiota², Naoya Ishizaka³, Shin Kawano¹, Yasushi Tamura⁴, Kher Shing Tan⁵, Kenichiro Imai⁶, Chie Motono⁶, Takatsugu Hirokawa⁷, Kentaro Taki⁸, Non Miyata⁹, Osamu Kuge⁹, Trevor Lithgow⁵, Toshiya Endo¹⁰

Affiliations

¹ Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.
² Organization for Promotion of Tenure Track, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki 889-2192, Japan; Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, Australia.
³ Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
⁴ Department of Material and Biological Chemistry, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan.
⁵ Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, Australia.
⁶ Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
⁷ Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan.
⁸ Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
⁹ Department of Chemistry, Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
¹⁰ Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan. Electronic address: tendo@cc.kyoto-su.ac.jp.

PMID: 30738703
DOI: 10.1016/j.molcel.2019.01.003

Abstract

Mitochondria import nearly all of their resident proteins from the cytosol, and the TOM complex functions as their entry gate. The TOM complex undergoes a dynamic conversion between the majority population of a three-channel gateway ("trimer") and the minor population that lacks Tom22 and has only two Tom40 channels ("dimer"). Here, we found that the porin Por1 acts as a sink to bind newly imported Tom22. This Por1 association thereby modulates Tom22 integration into the TOM complex, guaranteeing formation of the functional trimeric TOM complex. Por1 sequestration of Tom22 dissociated from the trimeric TOM complex also enhances the dimeric TOM complex, which is preferable for the import of TIM40/MIA-dependent proteins into mitochondria. Furthermore, Por1 appears to contribute to cell-cycle-dependent variation of the functional trimeric TOM complex by chaperoning monomeric Tom22, which arises from the cell-cycle-controlled variation of phosphorylated Tom6.

Keywords: TOM complex; Tom22; Tom40; Tom6; VDAC; mitochondria; porin; protein import.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Transport
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Cycle
HSP70 Heat-Shock Proteins / genetics
HSP70 Heat-Shock Proteins / metabolism
Mitochondria / genetics
Mitochondria / metabolism*
Mitochondrial Membrane Transport Proteins / genetics
Mitochondrial Membrane Transport Proteins / metabolism*
Mitochondrial Membranes / metabolism*
Mitochondrial Precursor Protein Import Complex Proteins
Phosphorylation
Porins / genetics
Porins / metabolism*
Protein Binding
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / growth & development
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*

Substances

Carrier Proteins
HSP70 Heat-Shock Proteins
MIA40 protein, S cerevisiae
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Por1 protein, S cerevisiae
Porins
Saccharomyces cerevisiae Proteins
TOM22 protein, S cerevisiae
TOM6 protein, S cerevisiae