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PMID: 18417609 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a novel protein MICS1 that is involved in maintenance of mitochondrial morphology and apoptotic release of cytochrome c.

Molecular biology of the cell ·Vol. 19 ·No. 6 ·2008-06-00 ·Pages 2597-608

Oka T, Sayano T, Tamai S, Yokota S, Kato H, Fujii G, Mihara K

Abstract

Mitochondrial morphology dynamically changes in a balance of membrane fusion and fission in response to the environment, cell cycle, and apoptotic stimuli. Here, we report that a novel mitochondrial protein, MICS1, is involved in mitochondrial morphology in specific cristae structures and the apoptotic release of cytochrome c from the mitochondria. MICS1 is an inner membrane protein with a cleavable presequence and multiple transmembrane segments and belongs to the Bi-1 super family. MICS1 down-regulation causes mitochondrial fragmentation and cristae disorganization and stimulates the release of proapoptotic proteins. Expression of the anti-apoptotic protein Bcl-XL does not prevent morphological changes of mitochondria caused by MICS1 down-regulation, indicating that MICS1 plays a role in maintaining mitochondrial morphology separately from the function in apoptotic pathways. MICS1 overproduction induces mitochondrial aggregation and partially inhibits cytochrome c release during apoptosis, regardless of the occurrence of Bax targeting. MICS1 is cross-linked to cytochrome c without disrupting membrane integrity. Thus, MICS1 facilitates the tight association of cytochrome c with the inner membrane. Furthermore, under low-serum condition, the delay in apoptotic release of cytochrome c correlates with MICS1 up-regulation without significant changes in mitochondrial morphology, suggesting that MICS1 individually functions in mitochondrial morphology and cytochrome c release.

MeSH Terms
Apoptosis Apoptosis Regulatory Proteins Cytochromes c/metabolism Down-Regulation HeLa Cells Humans Immunoprecipitation Intracellular Signaling Peptides and Proteins/metabolism Membrane Proteins/metabolism Mitochondria/metabolism,ultrastructure Mitochondrial Membranes/metabolism Mitochondrial Proteins/metabolism Permeability Protein Transport Serum Up-Regulation bcl-2-Associated X Protein/metabolism
Chemicals
Apoptosis Regulatory Proteins DIABLO protein, human GHITM protein, human Intracellular Signaling Peptides and Proteins Membrane Proteins Mitochondrial Proteins bcl-2-Associated X Protein Cytochromes c
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Oka Toshihiko
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. okat@cell.med.kyushu-u.ac.jp
Sayano Tomoko
Tamai Shoko
Yokota Sadaki
Kato Hiroki
Fujii Gen
Mihara Katsuyoshi
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e07-12-1205
Email
okat@cell.med.kyushu-u.ac.jp
Published
2008-06-00
Epub
2008-00-16
Pages
2597-608
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2397309
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e07-12-1205 PMC Full Text View journal details
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