Universität zu Köln

Saita, Shotaro ORCID: 0000-0002-7406-8361, Ishihara, Takaya, Maeda, Maki, Iemura, Shun-ichiro, Natsume, Tohru ORCID: 0000-0002-1510-2582, Mihara, Katsuyoshi and Ishihara, Naotada ORCID: 0000-0002-6305-7149 (2016). Distinct types of protease systems are involved in homeostasis regulation of mitochondrial morphology via balanced fusion and fission. Genes Cells, 21 (5). S. 408 - 425. HOBOKEN: WILEY. ISSN 1365-2443

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Abstract

Mitochondrial morphology is dynamically regulated by fusion and fission. Several GTPase proteins control fusion and fission, and posttranslational modifications of these proteins are important for the regulation. However, it has not been clarified how the fusion and fission is balanced. Here, we report the molecular mechanism to regulate mitochondrial morphology in mammalian cells. Ablation of the mitochondrial fission, by repression of Drp1 or Mff, or by over-expression of MiD49 or MiD51, results in a reduction in the fusion GTPase mitofusins (Mfn1 and Mfn2) in outer membrane and long form of OPA1 (L-OPA1) in inner membrane. RNAi- or CRISPR-induced ablation of Drp1 in HeLa cells enhanced the degradation of Mfns via the ubiquitin-proteasome system (UPS). We further found that UPS-related protein BAT3/BAG6, here we identified as Mfn2-interacting protein, was implicated in the turnover of Mfns in the absence of mitochondrial fission. Ablation of the mitochondrial fission also enhanced the proteolytic cleavage of L-OPA1 to soluble S-OPA1, and the OPA1 processing was reversed by inhibition of the inner membrane protease OMA1 independent on the mitochondrial membrane potential. Our findings showed that the distinct degradation systems of the mitochondrial fusion proteins in different locations are enhanced in response to the mitochondrial morphology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saita, Shotaro UNSPECIFIED orcid.org/0000-0002-7406-8361 UNSPECIFIED Ishihara, Takaya UNSPECIFIED UNSPECIFIED UNSPECIFIED Maeda, Maki UNSPECIFIED UNSPECIFIED UNSPECIFIED Iemura, Shun-ichiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Natsume, Tohru UNSPECIFIED orcid.org/0000-0002-1510-2582 UNSPECIFIED Mihara, Katsuyoshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ishihara, Naotada UNSPECIFIED orcid.org/0000-0002-6305-7149 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-277005
DOI:	10.1111/gtc.12351
Journal or Publication Title:	Genes Cells
Volume:	21
Number:	5
Page Range:	S. 408 - 425
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2443
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; TAIL-ANCHORED PROTEINS; M-AAA PROTEASE; EMBRYONIC-DEVELOPMENT; PROTEOLYTIC CLEAVAGE; MAMMALIAN HOMOLOGS; DRP1 RECRUITMENT; UBIQUITIN LIGASE; CYTOCHROME-C Multiple languages Cell Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27700