The VDAC2-BAK axis regulates peroxisomal membrane permeability

Ken-ichiro Hosoi, Non Miyata, Satoru Mukai, Satomi Furuki, Kanji Okumoto, Emily H. Cheng, Yukio Fujiki

研究成果: ジャーナルへの寄稿記事

20 引用 (Scopus)

抄録

Peroxisomal biogenesis disorders (PBDs) are fatal genetic diseases consisting of 14 complementation groups (CGs). We previously isolated a peroxisome-deficient Chinese hamster ovary cell mutant, ZP114, which belongs to none of these CGs. Using a functional screening strategy, VDAC2 was identified as rescuing the peroxisomal deficiency of ZP114 where VDAC2 expression was not detected. Interestingly, knockdown of BAK or overexpression of the BAK inhibitors BCL-XL and MCL-1 restored peroxisomal biogenesis in ZP114 cells. Although VDAC2 is not localized to the peroxisome, loss of VDAC2 shifts the localization of BAK from mitochondria to peroxisomes, resulting in peroxisomal deficiency. Introduction of peroxisome-targeted BAK harboring the Pex26p transmembrane region into wild-type cells resulted in the release of peroxisomal matrix proteins to cytosol. Moreover, overexpression of BAK activators PUMA and BIM permeabilized peroxisomes in a BAK-dependent manner. Collectively, these findings suggest that BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization.
元の言語英語
ページ(範囲)709-722
ジャーナルJournal of Cell Biology
216
発行部数3
DOI
出版物ステータス出版済み - 3 6 2017

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Peroxisomes
Permeability
Membranes
Peroxisomal Disorders
Inborn Genetic Diseases
Mitochondrial Membranes
Cricetulus
Cytosol
Ovary
Mitochondria
Proteins

これを引用

The VDAC2-BAK axis regulates peroxisomal membrane permeability. / Hosoi, Ken-ichiro; Miyata, Non; Mukai, Satoru; Furuki, Satomi; Okumoto, Kanji; Cheng, Emily H.; Fujiki, Yukio.

:: Journal of Cell Biology, 巻 216, 番号 3, 06.03.2017, p. 709-722.

研究成果: ジャーナルへの寄稿記事

Hosoi, K, Miyata, N, Mukai, S, Furuki, S, Okumoto, K, Cheng, EH & Fujiki, Y 2017, 'The VDAC2-BAK axis regulates peroxisomal membrane permeability', Journal of Cell Biology, 巻. 216, 番号 3, pp. 709-722. https://doi.org/10.1083/jcb.201605002
Hosoi, Ken-ichiro ; Miyata, Non ; Mukai, Satoru ; Furuki, Satomi ; Okumoto, Kanji ; Cheng, Emily H. ; Fujiki, Yukio. / The VDAC2-BAK axis regulates peroxisomal membrane permeability. :: Journal of Cell Biology. 2017 ; 巻 216, 番号 3. pp. 709-722.
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abstract = "Peroxisomal biogenesis disorders (PBDs) are fatal genetic diseases consisting of 14 complementation groups (CGs). We previously isolated a peroxisome-deficient Chinese hamster ovary cell mutant, ZP114, which belongs to none of these CGs. Using a functional screening strategy, VDAC2 was identified as rescuing the peroxisomal deficiency of ZP114 where VDAC2 expression was not detected. Interestingly, knockdown of BAK or overexpression of the BAK inhibitors BCL-XL and MCL-1 restored peroxisomal biogenesis in ZP114 cells. Although VDAC2 is not localized to the peroxisome, loss of VDAC2 shifts the localization of BAK from mitochondria to peroxisomes, resulting in peroxisomal deficiency. Introduction of peroxisome-targeted BAK harboring the Pex26p transmembrane region into wild-type cells resulted in the release of peroxisomal matrix proteins to cytosol. Moreover, overexpression of BAK activators PUMA and BIM permeabilized peroxisomes in a BAK-dependent manner. Collectively, these findings suggest that BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization.",
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AU - Miyata, Non

AU - Mukai, Satoru

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AU - Cheng, Emily H.

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N2 - Peroxisomal biogenesis disorders (PBDs) are fatal genetic diseases consisting of 14 complementation groups (CGs). We previously isolated a peroxisome-deficient Chinese hamster ovary cell mutant, ZP114, which belongs to none of these CGs. Using a functional screening strategy, VDAC2 was identified as rescuing the peroxisomal deficiency of ZP114 where VDAC2 expression was not detected. Interestingly, knockdown of BAK or overexpression of the BAK inhibitors BCL-XL and MCL-1 restored peroxisomal biogenesis in ZP114 cells. Although VDAC2 is not localized to the peroxisome, loss of VDAC2 shifts the localization of BAK from mitochondria to peroxisomes, resulting in peroxisomal deficiency. Introduction of peroxisome-targeted BAK harboring the Pex26p transmembrane region into wild-type cells resulted in the release of peroxisomal matrix proteins to cytosol. Moreover, overexpression of BAK activators PUMA and BIM permeabilized peroxisomes in a BAK-dependent manner. Collectively, these findings suggest that BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization.

AB - Peroxisomal biogenesis disorders (PBDs) are fatal genetic diseases consisting of 14 complementation groups (CGs). We previously isolated a peroxisome-deficient Chinese hamster ovary cell mutant, ZP114, which belongs to none of these CGs. Using a functional screening strategy, VDAC2 was identified as rescuing the peroxisomal deficiency of ZP114 where VDAC2 expression was not detected. Interestingly, knockdown of BAK or overexpression of the BAK inhibitors BCL-XL and MCL-1 restored peroxisomal biogenesis in ZP114 cells. Although VDAC2 is not localized to the peroxisome, loss of VDAC2 shifts the localization of BAK from mitochondria to peroxisomes, resulting in peroxisomal deficiency. Introduction of peroxisome-targeted BAK harboring the Pex26p transmembrane region into wild-type cells resulted in the release of peroxisomal matrix proteins to cytosol. Moreover, overexpression of BAK activators PUMA and BIM permeabilized peroxisomes in a BAK-dependent manner. Collectively, these findings suggest that BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization.

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